Description

Data processing and analysis of Visium data of subcutaneous white adipose tissue (scWAT) from 10 subjects at fasting state.

The standard Visium protocol (Rev A) as published by 10x Genomics was applied to generate the Visium sample libraries. Specific modifications of the protocol to adapt it for adipose tissue included using a section thickness of 16 µm and permeabilizing the tissue using a 15 min incubation with the permeabilization enzyme.

Sequencing of the Visium libraries was performed on the Illumina NovaSeq6000 platform, using a P4 flow cell, resulting in approximately 90M read-pairs per sample. The sequencing was performed by the National Genomics Infrastructure in Genomics Production Stockholm.

Processing of the FastQ sequencing files was performed using the Spaceranger (version 1.0.0) pipeline, mapping to the GRCh38-3.0.0 genome. Manual selection of spots to include in the analysis was performed using the Loupe Browser.

Analysis of the Spaceranger output data was performed using STUtility, which in turn makes use of the Seurat version 3, (3.1.5) R package.

The main data processing/analysis steps include the following:

  1. Initialize: Set up Seurat object and perform initial filtering of spots and genes
  2. QC: Further filter spots and genes based on specified criteria
  3. SCTransform: Peform normalization and scaling of the data using the 7000 most variable genes across the data points
  4. Dimensionality reduction: Independent Component Analysis (ICA) followed by Harmony (v 1.0) to remove subject an batch differences. The Harmony vectors, of which some uninformative vectors had been excluded, were used as input for UMAP and cluster analysis
  5. Clustering: Performed using the FindNeighbors() and FindClusters(algorithm = 1, resolution = k) (Louvain) functions. Clustering resolution k = 1.0 was selected after manual inspection of various resolution alternatives
  6. Marker genes: Cluster markers were identified using the FindMarkers() and FindAllMarkers(only.pos = TRUE, min.pct = 0.1, logfc.threshold = 0.15) functions





Initialize



Load necessary tables

Sample meta data

metadata <- read.table(file = file.path(DIR_DATA, "visium_sample_metadata.tsv"), sep = "\t", header = T, stringsAsFactors = F)
metadata_selected <- metadata[is.na(metadata$insulin_stim) | metadata$insulin_stim == 0, ]  # all baseline samples (no ins stim)
metadata_selected$seu_n <- seq( 1, dim(metadata_selected)[1] )

datatable(metadata_selected, rownames = F, caption = paste("Sample metadata"))



Gene annotations

gene_table <- read.table(file = file.path(DIR_DATA, "..", "gene_annotation", "gene_table.tsv"), sep = "\t", header = T, stringsAsFactors = F )



InfoTable

sample_select_ids <- metadata_selected[, "novaseq_id"]
data_proc <- "trimmed"
sample_dirs_all <- c()
sample_names_all <- c()
for (s in sample_select_ids){
  message("Fetching data path for sample ", s)
  sample_dirs <- grep(pattern = s, x = list.dirs(path = file.path(DIR_DATA), recursive = F, full.names = T), value = T)
  sample_dirs <- grep(pattern = data_proc, x = sample_dirs, value = T)
  sample_dirs_all <- c(sample_dirs_all, sample_dirs)
  
  sample_names <- grep(pattern = s, x = list.dirs(path = file.path(DIR_DATA), recursive = F, full.names = F), value = T)
  sample_names <- grep(pattern = data_proc, x = sample_names, value = T)
  sample_names_all <- c(sample_names_all, sample_names)
}

data_dirs <- paste0(sample_dirs_all, "/filtered_feature_bc_matrix.h5")
spot_dirs <- paste0(sample_dirs_all, "/spatial/tissue_positions_list.csv")
img_dirs <- paste0(sample_dirs_all, "/spatial/tissue_hires_image.png")
img_scale_dirs <- paste0(sample_dirs_all, "/spatial/scalefactors_json.json")

infoTable <- data.frame(samples = data_dirs,
                        spotfiles = spot_dirs,
                        imgs = img_dirs,
                        json = img_scale_dirs,
                        metadata_selected, 
                        stringsAsFactors = F)



Create Seurat object

Since we only have few cells per spot, we are a bit more gentle with the filtering compared to what is common for other tissue types.

se <- InputFromTable(infotable = infoTable, 
                      min.gene.count = 100, 
                      min.gene.spots = 5,
                      min.spot.count = 200,
                      platform="Visium")
## Using spotfiles to remove spots outside of tissue
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S42_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S44_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S46_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S48_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S49_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S50_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S51_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S52_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S54_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## Loading /Users/lovisa.franzen/Documents/ST_Adipose/scwat-st/scripts/../data/visium/S55_trimmed/filtered_feature_bc_matrix.h5 count matrix from a 'Visium' experiment
## 
## ------------- Filtering (not including images based filtering) -------------- 
##   Spots removed:  605  
##   Genes removed:  21468  
## Saving capture area ranges to Staffli object 
## After filtering the dimensions of the experiment is: [12070 genes, 28360 spots]



QC

se <- PercentageFeatureSet(se, pattern = "^MT-", col.name = "percent.mt")
se <- PercentageFeatureSet(se, pattern = "^MTRNR", col.name = "percent.MTRNR")
se <- PercentageFeatureSet(se, pattern = "^MALAT1", col.name = "percent.MALAT1")
se <- PercentageFeatureSet(se, pattern = "^RPS|^RPL", col.name = "percent.RP")
se <- PercentageFeatureSet(se, features = c("HBB", "HBA2", "HBA1"), col.name = "percent.HB.genes")
#' Subset/filter data before normalizing and scaling data. Remove high MT-content spots, and high HB-content spots
dim(se)
## [1] 12070 28360
paste("n spots with too high MT-content:", dim(subset(se[[]], percent.mt >= 40))[1] )
## [1] "n spots with too high MT-content: 244"
paste("n spots with too high HB-content:", dim(subset(se[[]], percent.HB.genes >= 10))[1] )
## [1] "n spots with too high HB-content: 179"
spots_mt <- rownames(subset(se[[]], percent.mt < 40))
spots_hb <- rownames(subset(se[[]], percent.HB.genes < 10))
spots <- intersect(spots_mt, spots_hb)

#' FILTER 1
se <- SubsetSTData(se, spots = spots)

#' Filter genes: Updated list
genes_remove <- grep("^HBB|^HBA|^MTRNR|^MT-|^MALAT1|^NEAT1|^RPS|^RPL", x = rownames(se), value = TRUE)

#' Filter gene types
gene_type_remove <- "antisense"  # c(grep(pattern = "pseudogene", x = unique(gene_table$gene_type), value = T), "antisense")
genes_remove_2 <- c(genes_remove, gene_table[gene_table$gene_type %in% gene_type_remove, "gene_name"])

paste("Removing", length(genes_remove), "genes due to specific selection")
## [1] "Removing 117 genes due to specific selection"
paste("Removing", length(intersect(rownames(se), genes_remove_2)), 
      "genes in total when excluding biotype 'antisense'")
## [1] "Removing 380 genes in total when excluding biotype 'antisense'"
#' Define genes to keep
genes_keep <- setdiff(rownames(se), genes_remove_2)

#' FILTER 2
se <- se[genes_keep, ]
dim(se)
## [1] 11690 27937



SCTransform

n_var_feat <- 7000
se <- SCTransform(se, variable.features.n = n_var_feat, verbose = F)



Dimensionality reduction

ICA

Warning: This step takes a long time to run due to the high number of spots and genes in the data

se <- RunICA(object = se, verbose = T)
## IC_ 1 
## Positive:  SAA1, AHNAK, LEP, HSP90AA1, SPTBN1, ITGB1, CRYAB, AKAP12, DDR2, GOLGA4 
##     PALMD, CCDC80, KIF5B, UTRN, CES1, PLIN4, SORBS1, CALM1, TNS1, ITIH5 
##     CAVIN1, GOLGB1, ITSN1, NCL, KTN1, CHRDL1, GPAM, HSP90B1, DST, MAP1B 
## Negative:  ADIRF, APOC1, ADH1B, FAU, APOE, GLUL, FASN, EIF1, FABP5, EEF1A1 
##     CFD, CIDEA, FABP4, COX7C, TTC36, UBA52, EEF2, CYB5A, RACK1, ATP5MC2 
##     ZFAND5, PRDX6, UQCRB, NACA, MZT2B, ATP5ME, SLC25A6, SNHG25, NDUFA4, TOMM7 
## IC_ 2 
## Positive:  AHNAK, HSP90AA1, SCD, SPTBN1, GOLGA4, DDR2, KTN1, ITGB1, CAVIN1, CCDC80 
##     DCN, NCL, TTC3, AKAP12, EIF3A, KIF5B, GOLGB1, MAP1B, ATRX, LEP 
##     HSP90B1, UTRN, EIF5B, CAST, IGFBP5, DST, CALD1, ANKRD12, MYCBP2, CSDE1 
## Negative:  G0S2, FABP4, FTL, MT1X, ADIRF, GPX4, DGAT2, CRYAB, PLIN4, RBP4 
##     MGST3, POLR2L, ATP5MD, COX7C, AGPAT2, LGALS1, UQCRH, COX6B1, RARRES2, GPD1 
##     OST4, NDUFA4, FAU, UQCR10, S100A11, UQCR11, UBL5, TSTD1, COX7B, FTH1 
## IC_ 3 
## Positive:  EGFL6, SAA1, CES1, TNMD, ASAH1, TMSB4X, MEGF9, CACNA2D1, COL3A1, AKR1C1 
##     CLU, AKR1C2, AKR1C3, ANXA5, STMN2, LEP, PALLD, SEMA3C, ITIH5, SNX10 
##     NPR3, VGLL3, SAA2, NPY1R, NQO1, UGP2, TUBB2A, LRMDA, SFRP2, PLIN2 
## Negative:  FASN, AKAP12, PABPC1, TNS1, GLUL, GPX3, ADH1B, PFKFB3, ADIRF, EEF1A1 
##     FADS1, CD81, HLA-B, HLA-A, PTMA, CXCL14, NNAT, UBA52, SCD, TF 
##     ACACB, MT1X, AQP7, SORBS1, CFD, FAU, NAP1L1, CD74, A2M, B2M 
## IC_ 4 
## Positive:  ACKR1, CD74, AQP1, VWF, RAMP3, PLVAP, HLA-B, HLA-E, HLA-DRA, IGFBP7 
##     PECAM1, HLA-DRB1, CTGF, IFITM3, HLA-DPA1, B2M, TAGLN, PLAT, HLA-A, IGFBP5 
##     ENG, EDN1, HLA-DPB1, TSPAN7, SPARCL1, IGFBP4, ACTA2, MLPH, KCTD12, IFITM2 
## Negative:  SAA1, FABP4, LEP, G0S2, PLIN1, CRYAB, GPAM, SCD, ADIPOQ, ACSL1 
##     PLIN4, PPP1R1A, MGST1, PRKAR2B, RBP4, GOLGA4, GPD1, SORBS1, GPX4, ITGB1 
##     SPTBN1, HSP90AA1, PLA2G16, AHNAK, AKAP12, AKR1C2, CAV2, TRDN, ADH1B, ALDH2 
## IC_ 5 
## Positive:  SAA1, AHNAK, SCD, ITGB1, HSP90AA1, LEP, SPTBN1, GPAM, DDR2, ACSL1 
##     PALMD, NCL, AKAP12, GOLGA4, CALD1, SORBS1, KTN1, CES1, KIF5B, PLIN4 
##     PTPN11, UTRN, TTC3, DST, UGP2, CAVIN1, MAP1B, MGST1, GPD1, MAP4 
## Negative:  RNASE1, C1QA, C1QB, LGMN, FOLR2, C1QC, LYVE1, SELENOP, F13A1, TYROBP 
##     CD74, STAB1, CD14, CSF1R, MARCO, CST3, CTSC, MRC1, FCGR2B, MS4A4A 
##     PLTP, FCGRT, MPEG1, FCER1G, MS4A6A, LILRB5, SLC40A1, TGFBI, CD68, FTL


Harmony

Integration of data from the different donors, and batch effect removal, using Harmony. Harmony is a method for integration of single cell RNA-seq data but we've seen promising use for it on ST data. It can easily be run together with Seurat using the RunHarmony() function.
http://htmlpreview.github.io/?https://github.com/immunogenomics/harmony/blob/master/docs/SeuratV3.html

*Korsunsky, I., Millard, N., Fan, J. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods 16, 1289–1296 (2019). https://doi-org.focus.lib.kth.se/10.1038/s41592-019-0619-0*

var_int <- c("date_exp", "subject_id")
se <- RunHarmony(object = se, group.by.vars = var_int, assay.use="SCT", reduction = "ica", plot_convergence = TRUE)


Dimension selction

Based on manual visual inspection of the vector loading for each harmony component, the most prominent and biologically relevant components were selected for further processing.

red_use <- "harmony"
dims_use <- 1:35


UMAP

nneigh <- 50
se <- RunUMAP(object = se, 
              reduction = red_use, 
              dims = dims_use,
              n.neighbors = nneigh)

se <- RunUMAP(object = se, 
              reduction = "ica", 
              dims = dims_use, 
              n.neighbors = nneigh,
              reduction.name = "umapICA",
              seed.use = 42)

se <- AddMetaData(se, se@reductions$umap@cell.embeddings, col.name = c("UMAP_1", "UMAP_2"))
paste("k (spots):", dim(se@reductions$umap@cell.embeddings)[1])
## [1] "k (spots): 27937"



Clustering

Finding neighbours by constructing a Shared Nearest Neighbor (SSN) Graph, and then cluster using a modularity optimizer.

Generate clusters

se <- FindNeighbors(object = se, verbose = T, reduction = red_use, dims = dims_use)

for (res in c(0, 0.2, seq(0.4, 1, 0.1), 1.2, 1.6, 2) ){
  print(res)
  se <- FindClusters(object = se, verbose = T, algorithm = 1, resolution = res)
}
## [1] 0
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 1.0000
## Number of communities: 21
## Elapsed time: 1 seconds
## [1] 0.2
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.9037
## Number of communities: 31
## Elapsed time: 1 seconds
## [1] 0.4
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.8334
## Number of communities: 34
## Elapsed time: 2 seconds
## [1] 0.5
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.8021
## Number of communities: 35
## Elapsed time: 2 seconds
## [1] 0.6
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.7741
## Number of communities: 36
## Elapsed time: 3 seconds
## [1] 0.7
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.7479
## Number of communities: 38
## Elapsed time: 2 seconds
## [1] 0.8
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.7337
## Number of communities: 38
## Elapsed time: 3 seconds
## [1] 0.9
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.7213
## Number of communities: 39
## Elapsed time: 3 seconds
## [1] 1
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.7103
## Number of communities: 40
## Elapsed time: 4 seconds
## [1] 1.2
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.6921
## Number of communities: 42
## Elapsed time: 4 seconds
## [1] 1.6
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.6639
## Number of communities: 44
## Elapsed time: 4 seconds
## [1] 2
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 27937
## Number of edges: 563101
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.6432
## Number of communities: 47
## Elapsed time: 4 seconds
res_use <- "SCT_snn_res.1"
se[["seurat_clusters"]] <- se[[res_use]]
se[["seurat_clusters"]] <- as.factor(as.numeric(as.character(se[[]]$seurat_clusters))+1)   #as.factor(as.numeric(se[[]]$seurat_clusters))
se <- SetIdent(se, value = "seurat_clusters")

n <- length( unique(as.character(se@meta.data$seurat_clusters)) )
print(paste("Number of clusters:", n))
## [1] "Number of clusters: 20"


Cluster annotations

cluster_anno <- c(
  "Unspecific 1",
  "Unspecific 2", 
  "Adipocyte 1", 
  "Adipocyte 2", 
  "Endothelial 1", 
  "Adipocyte 3", 
  "Preadipocyte 1", 
  "Immune: Mac-Mono-DC 1",
  "Preadipocyte 2", 
  "Immune: Mast cell", 
  "Preadipocyte 3",
  "Preadipocyte 4",
  "Immune: NK cell",
  "Endothelial 2",
  "Immune: Mac-Mono-DC 2",
  "Immune: Mac-Mono-DC 3",
  "Vascular 1",
  "Immune: B cell",
  "Vascular 2",
  "Immune: Mac-Mono-DC 4")

cluster_group <- c(
  "Unspecific", "Unspecific",
  "Adipocyte", "Adipocyte",
  "Vascular", 
  "Adipocyte",
  "Fibroblast/Pread",
  "Immune",
  "Fibroblast/Pread",
  "Immune",
  "Fibroblast/Pread",
  "Fibroblast/Pread",
  "Immune",
  "Vascular",
  "Immune", "Immune",
  "Vascular",
  "Immune",
  "Vascular",
  "Immune"
)

c_anno <- data.frame(seurat_clusters = as.numeric(seq(1, 20)),
                     cluster_anno = cluster_anno,
                     cluster_group = cluster_group,
                     stringsAsFactors = F)
c_anno <- c_anno[order(as.character(c_anno$cluster_anno)),]
cluster_anno <- NULL
cluster_group <- NULL

c_anno$cluster_color <- "#FFFFFF"
c_anno$color_group <- "white"

color_func_blue <- colorRampPalette(colors = c("#C6DBEF", "#075a84"))
color_func_orange <- colorRampPalette(colors = c("#F3E55C", "#E8602D"))
color_func_pink <- colorRampPalette(colors = c("#bfabc3", "#62376e"))
color_func_green <- colorRampPalette(colors = c("#a6dbbb", "#359566"))
color_func_purp <- colorRampPalette(colors = c("#ecd9f1", "#967bce"))

for( group in unique(c_anno$cluster_group) ){
  print(group)
  gs <- c_anno[c_anno$cluster_group == group, "cluster_group"]
  gs_l <- length(gs)
  c_add <- 1
  if(group == "Unspecific"){
    col_pal <- brewer.pal(gs_l+c_add+5, "Greys")[(2+c_add):(gs_l+c_add+1)]
    c_anno[c_anno$cluster_group == group, "color_group"] <- "grey"
  }
  if(group == "Adipocyte"){
    # col_pal <- (brewer.pal(gs_l+c_add, "RdPu")[(1+c_add):(gs_l+c_add)])
    col_pal <- color_func_pink(gs_l)
    c_anno[c_anno$cluster_group == group, "color_group"] <- "purple"
  }
  if(group == "Fibroblast/Pread"){
    # col_pal <- (brewer.pal(gs_l+c_add+1, "Oranges")[(1+c_add):(gs_l+c_add)])
    col_pal <- color_func_orange(gs_l)
    c_anno[c_anno$cluster_group == group, "color_group"] <- "orange"
  }
  if(group == "Immune"){
    # col_pal <- (brewer.pal(gs_l+c_add+1, "Blues")[(1+c_add):(gs_l+c_add)])
    col_pal <- color_func_blue(gs_l)
    c_anno[c_anno$cluster_group == group, "color_group"] <- "blue"
  }
  if(group == "Vascular"){
    # col_pal <- (brewer.pal(gs_l+c_add, "YlGn")[(1+c_add):(gs_l+c_add)])
    col_pal <- color_func_green(gs_l)
    c_anno[c_anno$cluster_group == group, "color_group"] <- "green"
  }
  print(col_pal)
  c_anno[c_anno$cluster_group == group, "cluster_color"] <- as.character(col_pal)
}
## [1] "Adipocyte"
## [1] "#BFABC3" "#907198" "#62376E"
## [1] "Vascular"
## [1] "#A6DBBB" "#80C39E" "#5AAC82" "#359566"
## [1] "Immune"
## [1] "#C6DBEF" "#A6C5DD" "#86B0CB" "#669AB9" "#4684A7" "#266F95" "#075A84"
## [1] "Fibroblast/Pread"
## [1] "#F3E55C" "#EFB84C" "#EB8C3C" "#E8602D"
## [1] "Unspecific"
## [1] "#D9D9D9" "#BDBDBD"
c_anno_long <- se[["seurat_clusters"]]
c_anno_long$barcode <- rownames(c_anno_long)
c_anno_long2 <- merge(c_anno_long, c_anno, by = "seurat_clusters", sort = F)
rownames(c_anno_long2) <- c_anno_long2$barcode
c_anno_long2 <- c_anno_long2[rownames(c_anno_long), ]

se <- AddMetaData(se, c_anno_long2[, -c(1:2)])
fname <- paste0(ANALYSIS_ID, ".clustering_annotations.csv")
write.csv(c_anno, file = file.path(DIR_RES, "tables", fname), row.names = F)

Cluster stats

cluster_prop <- se[[]]
cluster_prop <- cluster_prop %>% 
  group_by(subject_alias, seurat_clusters, condition, bmi) %>%
  dplyr::count()
cluster_prop <- as.data.frame(cluster_prop)
colnames(cluster_prop)[1] <- "subject"

subject_spot_count <- aggregate(cluster_prop$n, by=list(subject = cluster_prop$subject), FUN=sum)
colnames(subject_spot_count)[2] <- "total_spots"

cluster_prop <- merge(x = cluster_prop, y = subject_spot_count, by = c("subject"))
cluster_prop$cluster_pct_subject <- round((cluster_prop$n / cluster_prop$total_spots), digits = 3)*100

write.csv(cluster_prop, file = file.path(DIR_RES, "tables", paste0(ANALYSIS_ID, ".clustering_countspots.csv")), row.names = F)
datatable(cluster_prop, rownames = F, caption = paste("Cluster spot count and proportions"))

Adipocyte re-clustering

Re-clustering of only the adipocyte clusters in order get more refined clusters and marker gene lists.

spots_select <- rownames(subset(se[[]], cluster_group %in% "Adipocyte"))
se_adi <- SubsetSTData(se, spots = spots_select)

dim(se_adi)
## [1] 11690  6655
unique(se_adi$cluster_anno)
## [1] "Adipocyte 2" "Adipocyte 1" "Adipocyte 3"
# ICA
se_adi <- RunICA(object = se_adi, verbose = T)
## IC_ 1 
## Positive:  FTL, GPX4, G0S2, ADIRF, FTH1, PLIN4, MT1X, FAU, SAA1, LGALS1 
##     CRYAB, FHL1, OST4, ATP5MD, SERF2, SNHG25, UBA52, COX7C, POLR2L, S100A11 
##     TMSB10, NDUFA4, UQCR11, GPD1, TOMM7, PPP1R14A, AGPAT2, LIPE, COX6B1, S100A6 
## Negative:  AHNAK, SPTBN1, HSP90AA1, SCD, ITGB1, GPAM, KTN1, GOLGA4, GOLGB1, AKAP12 
##     DDR2, UTRN, DMD, ATRX, HSP90B1, EIF3A, NCL, ACSL1, UACA, DST 
##     KIF5B, SYNM, PDE3B, EIF5B, TTC3, CALD1, PRKAR2B, DYNC1H1, HMGB1, MAP4 
## IC_ 2 
## Positive:  ADH1B, ADIRF, FAU, TTC36, APOE, APOC1, GLUL, FASN, FABP5, CFD 
##     CIDEA, EIF1, EEF1A1, FABP4, COX7C, EEF2, C6, ZFAND5, RACK1, PRDX6 
##     UBA52, ATP5ME, ATP5MC2, CYB5A, NACA, UQCRB, SNHG25, PFDN5, TOMM7, WNT3 
## Negative:  SAA1, LEP, AHNAK, SAA2, SPTBN1, DDR2, PLIN4, HSP90AA1, CRYAB, SORBS1 
##     ITGB1, AKAP12, GOLGA4, CES1, CCDC80, CCND1, MAP1B, ITIH5, PALMD, TNS1 
##     KIF5B, CAVIN1, UTRN, PTPN11, NCL, ITSN1, GPAM, KTN1, SCD, SEPT11 
## IC_ 3 
## Positive:  AHNAK, DDR2, AKAP12, CAVIN1, TNS1, SPTBN1, FASN, ITGB1, MAP1B, KTN1 
##     HSP90AB1, LEP, ADH1B, DPT, HSP90AA1, MTURN, HMGB1, SEC62, GSN, TXNIP 
##     RTN4RL1, EIF3A, EIF5B, SORBS1, GOLGA4, SCD, HSP90B1, WDR60, DMD, ROCK2 
## Negative:  SAA2, SAA1, RBP4, SAA4, HP, PLA2G2A, FTL, FTH1, FABP4, COX6B1 
##     G0S2, UQCRQ, POLR2L, ATP6V1F, C4orf19, GPX4, COX7A2, COX6C, MGST1, OST4 
##     NMB, RCAN2, KRT14, NDUFB1, DEFB132, ATP5PO, MT1X, LY86, EEF2, TSPO 
## IC_ 4 
## Positive:  SAA1, EGFL6, CES1, SAA2, ASAH1, TNMD, MEGF9, AKR1C1, PLIN4, AKR1C3 
##     AKR1C2, COL3A1, CACNA2D1, TMSB4X, ITIH5, NPY1R, PCK1, CLU, CD248, MCAM 
##     SEMA3C, PLIN2, SNX10, TUBB2A, ANXA5, SFRP2, TPM2, DGAT2, NPR3, STMN2 
## Negative:  TNS1, AKAP12, PABPC1, SORBS1, FASN, EEF1A1, NAP1L1, GPX3, ADIRF, EIF4B 
##     GLUL, ADH1B, PRKAR2B, ANP32B, FADS1, PTMA, FAU, TF, ST13, ITSN1 
##     UBA52, PFKFB3, NSA2, HLA-B, AHNAK, TOMM7, SPX, RACK1, GYG2, DCN 
## IC_ 5 
## Positive:  SCD, SAA1, GPAM, FASN, DGAT2, PLIN4, PLIN1, ACSL1, SAA2, RBP4 
##     TF, ACACB, AGPAT2, XIST, TRDN, IGF1, ADIPOQ, CES1, MGLL, CEBPA 
##     ELOVL5, SLC16A7, PCK1, FZD4, ELOVL6, ELMOD3, THRSP, G0S2, GPD1, PTPRF 
## Negative:  FTH1, MAP1B, DPT, TMSB4X, FTL, CAVIN1, ITGB1, SPTBN1, MAP4, EGFL6 
##     DDR2, CSDE1, MTURN, EEF1A1, EIF1AY, AHNAK, CCDC80, SYNPO, S100A6, CLSTN2 
##     PTPN11, TMSB10, CRYAB, AKAP12, YBX1, S100A10, LEP, PTMA, PLAC9, SORBS1
# Harmony
var_int <- c("date_exp", "subject_id")
se_adi <- RunHarmony(object = se_adi, group.by.vars = var_int, assay.use="SCT", reduction = "ica", plot_convergence = TRUE)

red_use <- "harmony"
dims_use_adi <- 1:13
se_adi <- FindNeighbors(object = se_adi, verbose = T, reduction = red_use, dims = dims_use_adi)

for (res in 0.5) {
  print(res)
  se_adi <- FindClusters(object = se_adi, verbose = T, algorithm = 1, resolution = res)
}
## [1] 0.5
## Modularity Optimizer version 1.3.0 by Ludo Waltman and Nees Jan van Eck
## 
## Number of nodes: 6655
## Number of edges: 175082
## 
## Running Louvain algorithm...
## Maximum modularity in 10 random starts: 0.6537
## Number of communities: 5
## Elapsed time: 0 seconds
res_use <- "SCT_snn_res.0.5"
se_adi[["seurat_clusters"]] <- se_adi[[res_use]]
se_adi[["seurat_clusters"]] <- as.factor(as.numeric(as.character(se_adi[[]]$seurat_clusters))+1)
se_adi <- SetIdent(se_adi, value = "seurat_clusters")

n <- length( unique(as.character(se_adi@meta.data$seurat_clusters)) )
print(paste("Number of clusters:", n))
## [1] "Number of clusters: 5"
print("Cluster sizes (n spots per cluster):")
## [1] "Cluster sizes (n spots per cluster):"
cluster_count_adi <- se_adi[["seurat_clusters"]] %>%
  group_by(seurat_clusters) %>%
  dplyr::count() %>%
  dplyr::arrange(desc(n))
cluster_count_adi$pct <- round(cluster_count_adi$n / sum(cluster_count_adi$n), digits = 3) * 100
cluster_count_adi
## # A tibble: 5 x 3
## # Groups:   seurat_clusters [5]
##   seurat_clusters     n   pct
##   <fct>           <int> <dbl>
## 1 1                1886  28.3
## 2 2                1569  23.6
## 3 3                1496  22.5
## 4 4                1103  16.6
## 5 5                 601   9



Cluster marker genes

Cluster DEA

LogFC cut-off 0.15

logf_thr <- 0.15
cluster_calc_de <- unique(sort(as.numeric(as.character(subset(cluster_prop, n>3)$seurat_clusters))))
markers_seu_clusters <- list()
for( i in cluster_calc_de ) {
  print(paste("Finding markers for cluster", i))
  c <- paste0("cluster_", i)
  
  markers_seu_clusters[[c]] <- FindMarkers(se, ident.1 = as.character(i), logfc.threshold = logf_thr)
}
## [1] "Finding markers for cluster 1"
## [1] "Finding markers for cluster 2"
## [1] "Finding markers for cluster 3"
## [1] "Finding markers for cluster 4"
## [1] "Finding markers for cluster 5"
## [1] "Finding markers for cluster 6"
## [1] "Finding markers for cluster 7"
## [1] "Finding markers for cluster 8"
## [1] "Finding markers for cluster 9"
## [1] "Finding markers for cluster 10"
## [1] "Finding markers for cluster 11"
## [1] "Finding markers for cluster 12"
## [1] "Finding markers for cluster 13"
## [1] "Finding markers for cluster 14"
## [1] "Finding markers for cluster 15"
## [1] "Finding markers for cluster 16"
## [1] "Finding markers for cluster 17"
## [1] "Finding markers for cluster 18"
## [1] "Finding markers for cluster 19"
## [1] "Finding markers for cluster 20"
top_n_genes <- 10
logf_thr <- 0.15

se_markers <- FindAllMarkers(se, 
                             only.pos = TRUE, 
                             min.pct = 0.1, 
                             logfc.threshold = logf_thr
                             )

se_markers$pct.diff <- se_markers$pct.1 - se_markers$pct.2
se_markers_top <- se_markers %>% 
  group_by(as.numeric(cluster)) %>% 
  dplyr::top_n(n = top_n_genes, wt = avg_logFC)

se_markers_top <- se_markers_top[, c("gene", "cluster", "avg_logFC", "pct.1", "pct.2", "pct.diff", "p_val", "p_val_adj")]
datatable(se_markers_top, rownames = F, caption = paste("Top", top_n_genes, "marker genes for the computed Seurat clusters"))
fname <- paste0(ANALYSIS_ID, ".markers_clusterdea.xlsx")

sheets <- list()
sheets["top_markers_all_clusters"] <- list(as.data.frame(se_markers_top))
for (i in 1:length(markers_seu_clusters)){
  c_name <- names(markers_seu_clusters[i])
  c_data <- markers_seu_clusters[[i]]
  c_names <- colnames(c_data)
  c_data$gene <- rownames(c_data)
  c_data <- c_data[, c("gene", c_names)]

  sheets[c_name] <- list(c_data)
}

write_xlsx(
  x = sheets,
  path = file.path(DIR_RES, "tables", fname),
  col_names = TRUE,
  format_headers = TRUE
)



ALL genes (no cut-off)

logf_thr <- 0
cluster_calc_de <- unique(sort(as.numeric(as.character(subset(cluster_prop, n>3)$seurat_clusters))))
markers_seu_clusters_all <- list()
for( i in cluster_calc_de ) {
  print(paste("Finding markers for cluster", i))
  c <- paste0("cluster_", i)
  
  markers_seu_clusters_all[[c]] <- FindMarkers(se, ident.1 = as.character(i), logfc.threshold = logf_thr)
}
## [1] "Finding markers for cluster 1"
## [1] "Finding markers for cluster 2"
## [1] "Finding markers for cluster 3"
## [1] "Finding markers for cluster 4"
## [1] "Finding markers for cluster 5"
## [1] "Finding markers for cluster 6"
## [1] "Finding markers for cluster 7"
## [1] "Finding markers for cluster 8"
## [1] "Finding markers for cluster 9"
## [1] "Finding markers for cluster 10"
## [1] "Finding markers for cluster 11"
## [1] "Finding markers for cluster 12"
## [1] "Finding markers for cluster 13"
## [1] "Finding markers for cluster 14"
## [1] "Finding markers for cluster 15"
## [1] "Finding markers for cluster 16"
## [1] "Finding markers for cluster 17"
## [1] "Finding markers for cluster 18"
## [1] "Finding markers for cluster 19"
## [1] "Finding markers for cluster 20"
fname <- paste0(ANALYSIS_ID, ".markers_clusterdea_ALL.xlsx")

sheets <- list()
for (i in 1:length(markers_seu_clusters_all)){
  c_name <- names(markers_seu_clusters_all[i])
  c_data <- markers_seu_clusters_all[[i]]
  c_names <- colnames(c_data)
  c_data$gene <- rownames(c_data)
  c_data <- c_data[, c("gene", c_names)]

  sheets[c_name] <- list(c_data)
}

write_xlsx(
  x = sheets,
  path = file.path(DIR_RES, "tables", fname),
  col_names = TRUE,
  format_headers = TRUE
)




Cluster DEA of adipocyte re-clustering

logf_thr <- 0

cluster_calc_de_adi <- sort(as.numeric(as.character(subset(cluster_count_adi, n>3)$seurat_clusters)))
markers_seu_clusters_adi <- list()
for( i in cluster_calc_de_adi ) {
  print(paste("Finding markers for cluster", i))
  c <- paste0("cluster_", i)
  
  markers_seu_clusters_adi[[c]] <- FindMarkers(se_adi, ident.1 = as.character(i), logfc.threshold = logf_thr)
}
## [1] "Finding markers for cluster 1"
## [1] "Finding markers for cluster 2"
## [1] "Finding markers for cluster 3"
## [1] "Finding markers for cluster 4"
## [1] "Finding markers for cluster 5"
top_n_genes <- 10
logf_thr <- 0.15

se_markers_adi <- FindAllMarkers(se_adi, only.pos = TRUE, min.pct = 0.1, logfc.threshold = logf_thr)

se_markers_adi$pct.diff <- se_markers_adi$pct.1 - se_markers_adi$pct.2
se_markers_adi_top <- se_markers_adi %>% 
  group_by(cluster) %>% 
  dplyr::top_n(n = top_n_genes, wt = avg_logFC)

se_markers_adi_top <- se_markers_adi_top[, c("gene", "cluster", "avg_logFC", "pct.1", "pct.2", "pct.diff", "p_val", "p_val_adj")]
datatable(se_markers_adi_top, rownames = F, caption = paste("Top", top_n_genes, "marker genes for the computed Seurat clusters"))
fname <- paste0(ANALYSIS_ID, "_adipocytes-reclust.markers_clusterdea.xlsx")

sheets <- list()
sheets["top_markers_all_clusters"] <- list(as.data.frame(se_markers_adi_top))
for (i in 1:length(markers_seu_clusters_adi)){
  c_name <- names(markers_seu_clusters_adi[i])
  c_data <- markers_seu_clusters_adi[[i]]
  c_names <- colnames(c_data)
  c_data$gene <- rownames(c_data)
  c_data <- c_data[, c("gene", c_names)]

  sheets[c_name] <- list(c_data)
}

write_xlsx(
  x = sheets,
  path = file.path(DIR_RES, "tables", fname),
  col_names = TRUE,
  format_headers = TRUE
)



Pathway enrichment

Marker gene pathways enrichment analysis for each cluster.

pw_results_go <- list()
pw_results_ra <- list()
for(c in names(markers_seu_clusters)){  #  names(markers_seu_clusters)
  d <- NULL
  d <- markers_seu_clusters[[c]]
  d <- subset(d, avg_logFC>0 & p_val_adj<0.05)
  d$gene_name <- rownames(d)
  eg = clusterProfiler::bitr(d$gene_name, fromType="SYMBOL", toType="ENTREZID", OrgDb="org.Hs.eg.db")
  rownames(eg) <- eg$SYMBOL
  colnames(eg) <- c("gene_name", "gene_entrez")
  
  d <- merge(d, eg, by = "gene_name", all = T)
  rownames(d) <- d$gene_name
  
  print(c)
  print(d$gene_name)
  print("---------------------------------")
  if( dim(d)[1] > 0 ) {
    pw_genes <- d$gene_entrez[!is.na(d$gene_entrez)]
    pw <- clusterProfiler::enrichGO(pw_genes, OrgDb="org.Hs.eg.db")
    pw_ra <- enrichPathway(pw_genes)
    
    pw_results_go[[c]] <- pw
    pw_results_ra[[c]] <- pw_ra
    
    if(!is.null(pw)) {
      print("GO Enrichment: ")
      print(subset(pw@result, p.adjust<0.05))
      print("---------------------------------")
    } else {
      print("No GO Enrichment available for gene set.")
    }
    if(!is.null(pw_ra)) {
      print("Reactome Enrichment: ")
      print(subset(pw_ra@result, p.adjust<0.05))
      print("---------------------------------")
    } else {
      print("No Reactome Enrichment available for gene set.")
    }
  } else {
    print("Not enough genes to perform analysis --- Skipping cluster!")
  }
  print("==================================")
}
## Loading required package: org.Hs.eg.db
## Loading required package: AnnotationDbi
## 
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_1"
## [1] "ADIRF"
## [1] "---------------------------------"
## No gene set have size > 10 ...
## --> return NULL...
## [1] "No GO Enrichment available for gene set."
## [1] "Reactome Enrichment: "
##                        ID
## R-HSA-381340 R-HSA-381340
##                                                                Description
## R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
##              GeneRatio  BgRatio      pvalue    p.adjust qvalue geneID Count
## R-HSA-381340       1/1 84/10654 0.007884363 0.007884363     NA  10974     1
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_2"
## [1] "AHNAK"  "DST"    "ITGB1"  "SPTBN1"
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                                        Description
## GO:0050839 GO:0050839                     cell adhesion molecule binding
## GO:0045296 GO:0045296                                   cadherin binding
## GO:0003779 GO:0003779                                      actin binding
## GO:0005178 GO:0005178                                   integrin binding
## GO:0097493 GO:0097493 structural molecule activity conferring elasticity
## GO:0044548 GO:0044548                               S100 protein binding
## GO:0051010 GO:0051010                       microtubule plus-end binding
## GO:0030506 GO:0030506                                    ankyrin binding
## GO:0001968 GO:0001968                                fibronectin binding
## GO:0043236 GO:0043236                                    laminin binding
## GO:0019956 GO:0019956                                  chemokine binding
## GO:0015026 GO:0015026                                coreceptor activity
## GO:0050840 GO:0050840                       extracellular matrix binding
## GO:0098631 GO:0098631                    cell adhesion mediator activity
## GO:0005518 GO:0005518                                   collagen binding
## GO:0001618 GO:0001618                            virus receptor activity
## GO:0104005 GO:0104005                        hijacked molecular function
## GO:0005200 GO:0005200             structural constituent of cytoskeleton
## GO:0002020 GO:0002020                                   protease binding
## GO:0019955 GO:0019955                                   cytokine binding
## GO:0008022 GO:0008022                         protein C-terminus binding
##            GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## GO:0050839       4/4 499/17697 6.247649e-07 1.561912e-05 1.972942e-06
## GO:0045296       3/4 331/17697 2.557950e-05 3.197438e-04 4.038869e-05
## GO:0003779       3/4 431/17697 5.634903e-05 4.695753e-04 5.931477e-05
## GO:0005178       2/4 132/17697 3.280638e-04 2.050399e-03 2.589977e-04
## GO:0097493       1/4  11/17697 2.484190e-03 1.242095e-02 1.568962e-03
## GO:0044548       1/4  15/17697 3.386384e-03 1.370447e-02 1.731091e-03
## GO:0051010       1/4  17/17697 3.837251e-03 1.370447e-02 1.731091e-03
## GO:0030506       1/4  20/17697 4.513265e-03 1.410395e-02 1.781552e-03
## GO:0001968       1/4  27/17697 6.089292e-03 1.634810e-02 2.065024e-03
## GO:0043236       1/4  29/17697 6.539242e-03 1.634810e-02 2.065024e-03
## GO:0019956       1/4  32/17697 7.213880e-03 1.639518e-02 2.070970e-03
## GO:0015026       1/4  44/17697 9.908997e-03 2.064374e-02 2.607631e-03
## GO:0050840       1/4  57/17697 1.282251e-02 2.369674e-02 2.993272e-03
## GO:0098631       1/4  59/17697 1.327017e-02 2.369674e-02 2.993272e-03
## GO:0005518       1/4  67/17697 1.505930e-02 2.444527e-02 3.087823e-03
## GO:0001618       1/4  74/17697 1.662278e-02 2.444527e-02 3.087823e-03
## GO:0104005       1/4  74/17697 1.662278e-02 2.444527e-02 3.087823e-03
## GO:0005200       1/4 102/17697 2.285812e-02 3.174739e-02 4.010196e-03
## GO:0002020       1/4 128/17697 2.862148e-02 3.577685e-02 4.519181e-03
## GO:0019955       1/4 128/17697 2.862148e-02 3.577685e-02 4.519181e-03
## GO:0008022       1/4 187/17697 4.160529e-02 4.953011e-02 6.256435e-03
##                         geneID Count
## GO:0050839 79026/667/3688/6711     4
## GO:0045296     79026/3688/6711     3
## GO:0003779       667/3688/6711     3
## GO:0005178            667/3688     2
## GO:0097493               79026     1
## GO:0044548               79026     1
## GO:0051010                 667     1
## GO:0030506                6711     1
## GO:0001968                3688     1
## GO:0043236                3688     1
## GO:0019956                3688     1
## GO:0015026                3688     1
## GO:0050840                3688     1
## GO:0098631                3688     1
## GO:0005518                3688     1
## GO:0001618                3688     1
## GO:0104005                3688     1
## GO:0005200                6711     1
## GO:0002020                3688     1
## GO:0019955                3688     1
## GO:0008022                 667     1
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1500931 R-HSA-1500931
## R-HSA-446728   R-HSA-446728
## R-HSA-373760   R-HSA-373760
## R-HSA-1474244 R-HSA-1474244
## R-HSA-446107   R-HSA-446107
## R-HSA-75892     R-HSA-75892
## R-HSA-446353   R-HSA-446353
## R-HSA-416700   R-HSA-416700
## R-HSA-445144   R-HSA-445144
## R-HSA-373753   R-HSA-373753
## R-HSA-210991   R-HSA-210991
## R-HSA-3000170 R-HSA-3000170
## R-HSA-3000157 R-HSA-3000157
## R-HSA-8874081 R-HSA-8874081
## R-HSA-445095   R-HSA-445095
## R-HSA-2129379 R-HSA-2129379
## R-HSA-8875878 R-HSA-8875878
## R-HSA-1566948 R-HSA-1566948
## R-HSA-3000171 R-HSA-3000171
## R-HSA-2022090 R-HSA-2022090
## R-HSA-375165   R-HSA-375165
## R-HSA-373755   R-HSA-373755
## R-HSA-3000178 R-HSA-3000178
## R-HSA-6806834 R-HSA-6806834
## R-HSA-216083   R-HSA-216083
## R-HSA-1474290 R-HSA-1474290
## R-HSA-6807878 R-HSA-6807878
## R-HSA-6785807 R-HSA-6785807
##                                                                Description
## R-HSA-1500931                                      Cell-Cell communication
## R-HSA-446728                                    Cell junction organization
## R-HSA-373760                                            L1CAM interactions
## R-HSA-1474244                            Extracellular matrix organization
## R-HSA-446107                                 Type I hemidesmosome assembly
## R-HSA-75892                          Platelet Adhesion to exposed collagen
## R-HSA-446353                        Cell-extracellular matrix interactions
## R-HSA-416700                                 Other semaphorin interactions
## R-HSA-445144                                     Signal transduction by L1
## R-HSA-373753                                   Nephrin family interactions
## R-HSA-210991                                          Basigin interactions
## R-HSA-3000170                                        Syndecan interactions
## R-HSA-3000157                                         Laminin interactions
## R-HSA-8874081                                 MET activates PTK2 signaling
## R-HSA-445095                           Interaction between L1 and Ankyrins
## R-HSA-2129379                     Molecules associated with elastic fibres
## R-HSA-8875878                                   MET promotes cell motility
## R-HSA-1566948                                      Elastic fibre formation
## R-HSA-3000171                       Non-integrin membrane-ECM interactions
## R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures
## R-HSA-375165                         NCAM signaling for neurite out-growth
## R-HSA-373755                                       Semaphorin interactions
## R-HSA-3000178                                            ECM proteoglycans
## R-HSA-6806834                                             Signaling by MET
## R-HSA-216083                            Integrin cell surface interactions
## R-HSA-1474290                                           Collagen formation
## R-HSA-6807878                          COPI-mediated anterograde transport
## R-HSA-6785807                   Interleukin-4 and Interleukin-13 signaling
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1500931       3/3 129/10654 1.734553e-06 7.285123e-05 1.825845e-05
## R-HSA-446728        2/3  91/10654 2.152755e-04 4.520786e-03 1.133029e-03
## R-HSA-373760        2/3 119/10654 3.684459e-04 5.158243e-03 1.292793e-03
## R-HSA-1474244       2/3 301/10654 2.342180e-03 2.437276e-02 6.108460e-03
## R-HSA-446107        1/3  11/10654 3.094521e-03 2.437276e-02 6.108460e-03
## R-HSA-75892         1/3  15/10654 4.218217e-03 2.437276e-02 6.108460e-03
## R-HSA-446353        1/3  18/10654 5.060435e-03 2.437276e-02 6.108460e-03
## R-HSA-416700        1/3  19/10654 5.341068e-03 2.437276e-02 6.108460e-03
## R-HSA-445144        1/3  21/10654 5.902177e-03 2.437276e-02 6.108460e-03
## R-HSA-373753        1/3  23/10654 6.463075e-03 2.437276e-02 6.108460e-03
## R-HSA-210991        1/3  25/10654 7.023762e-03 2.437276e-02 6.108460e-03
## R-HSA-3000170       1/3  27/10654 7.584237e-03 2.437276e-02 6.108460e-03
## R-HSA-3000157       1/3  30/10654 8.424555e-03 2.437276e-02 6.108460e-03
## R-HSA-8874081       1/3  30/10654 8.424555e-03 2.437276e-02 6.108460e-03
## R-HSA-445095        1/3  31/10654 8.704556e-03 2.437276e-02 6.108460e-03
## R-HSA-2129379       1/3  38/10654 1.066308e-02 2.799060e-02 7.015187e-03
## R-HSA-8875878       1/3  41/10654 1.150166e-02 2.841587e-02 7.121773e-03
## R-HSA-1566948       1/3  45/10654 1.261903e-02 2.944441e-02 7.379551e-03
## R-HSA-3000171       1/3  59/10654 1.652319e-02 3.473255e-02 8.704901e-03
## R-HSA-2022090       1/3  61/10654 1.708008e-02 3.473255e-02 8.704901e-03
## R-HSA-375165        1/3  63/10654 1.763677e-02 3.473255e-02 8.704901e-03
## R-HSA-373755        1/3  65/10654 1.819324e-02 3.473255e-02 8.704901e-03
## R-HSA-3000178       1/3  76/10654 2.125010e-02 3.864469e-02 9.685387e-03
## R-HSA-6806834       1/3  79/10654 2.208268e-02 3.864469e-02 9.685387e-03
## R-HSA-216083        1/3  85/10654 2.374644e-02 3.989401e-02 9.998499e-03
## R-HSA-1474290       1/3  90/10654 2.513145e-02 4.059696e-02 1.017468e-02
## R-HSA-6807878       1/3 101/10654 2.817388e-02 4.382604e-02 1.098397e-02
## R-HSA-6785807       1/3 108/10654 3.010667e-02 4.516001e-02 1.131830e-02
##                      geneID Count
## R-HSA-1500931 667/3688/6711     3
## R-HSA-446728       667/3688     2
## R-HSA-373760      3688/6711     2
## R-HSA-1474244      667/3688     2
## R-HSA-446107            667     1
## R-HSA-75892            3688     1
## R-HSA-446353           3688     1
## R-HSA-416700           3688     1
## R-HSA-445144           3688     1
## R-HSA-373753           6711     1
## R-HSA-210991           3688     1
## R-HSA-3000170          3688     1
## R-HSA-3000157          3688     1
## R-HSA-8874081          3688     1
## R-HSA-445095           6711     1
## R-HSA-2129379          3688     1
## R-HSA-8875878          3688     1
## R-HSA-1566948          3688     1
## R-HSA-3000171          3688     1
## R-HSA-2022090           667     1
## R-HSA-375165           6711     1
## R-HSA-373755           3688     1
## R-HSA-3000178          3688     1
## R-HSA-6806834          3688     1
## R-HSA-216083           3688     1
## R-HSA-1474290           667     1
## R-HSA-6807878          6711     1
## R-HSA-6785807          3688     1
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_3"
##  [1] "CAVIN1" "CCND1"  "CRTAP"  "CSDE1"  "DDR2"   "FTH1"   "FTL"    "HSPB6" 
##  [9] "LEP"    "MAP4"   "MTURN"  "PABPC1" "PTMA"   "PTPN11" "SEC62"  "SORBS1"
## [17] "SPTBN1" "TNS1"  
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0004322 GO:0004322
## GO:0016724 GO:0016724
## GO:0008199 GO:0008199
## GO:0016722 GO:0016722
## GO:0051428 GO:0051428
## GO:0005158 GO:0005158
## GO:0008198 GO:0008198
## GO:0005070 GO:0005070
## GO:0035591 GO:0035591
## GO:0003779 GO:0003779
##                                                                  Description
## GO:0004322                                              ferroxidase activity
## GO:0016724 oxidoreductase activity, oxidizing metal ions, oxygen as acceptor
## GO:0008199                                               ferric iron binding
## GO:0016722                     oxidoreductase activity, oxidizing metal ions
## GO:0051428                                  peptide hormone receptor binding
## GO:0005158                                          insulin receptor binding
## GO:0008198                                              ferrous iron binding
## GO:0005070                                          SH3/SH2 adaptor activity
## GO:0035591                                        signaling adaptor activity
## GO:0003779                                                     actin binding
##            GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## GO:0004322      2/17  10/17697 3.890835e-05 0.0009980834 0.0005669981
## GO:0016724      2/17  10/17697 3.890835e-05 0.0009980834 0.0005669981
## GO:0008199      2/17  11/17697 4.752778e-05 0.0009980834 0.0005669981
## GO:0016722      2/17  19/17697 1.471017e-04 0.0020829876 0.0011833180
## GO:0051428      2/17  21/17697 1.804472e-04 0.0020829876 0.0011833180
## GO:0005158      2/17  22/17697 1.983798e-04 0.0020829876 0.0011833180
## GO:0008198      2/17  24/17697 2.367575e-04 0.0021308177 0.0012104896
## GO:0005070      2/17  52/17697 1.119621e-03 0.0088170173 0.0050088319
## GO:0035591      2/17  80/17697 2.626354e-03 0.0183844765 0.0104439800
## GO:0003779      3/17 431/17697 7.565746e-03 0.0476642024 0.0270774082
##                     geneID Count
## GO:0004322       2495/2512     2
## GO:0016724       2495/2512     2
## GO:0008199       2495/2512     2
## GO:0016722       2495/2512     2
## GO:0051428       3952/5781     2
## GO:0005158      5781/10580     2
## GO:0008198       2495/2512     2
## GO:0005070      5781/10580     2
## GO:0035591      5781/10580     2
## GO:0003779 10580/6711/7145     3
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-2586552 R-HSA-2586552
## R-HSA-8934593 R-HSA-8934593
## R-HSA-3000480 R-HSA-3000480
## R-HSA-2173782 R-HSA-2173782
## R-HSA-432722   R-HSA-432722
## R-HSA-917937   R-HSA-917937
##                                                        Description GeneRatio
## R-HSA-2586552                                  Signaling by Leptin      2/11
## R-HSA-8934593          Regulation of RUNX1 Expression and Activity      2/11
## R-HSA-3000480                      Scavenging by Class A Receptors      2/11
## R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors      2/11
## R-HSA-432722                   Golgi Associated Vesicle Biogenesis      2/11
## R-HSA-917937                             Iron uptake and transport      2/11
##                BgRatio       pvalue    p.adjust      qvalue    geneID Count
## R-HSA-2586552 11/10654 5.303572e-05 0.008167501 0.004689474 3952/5781     2
## R-HSA-8934593 17/10654 1.307003e-04 0.008426434 0.004838144  595/5781     2
## R-HSA-3000480 19/10654 1.641513e-04 0.008426434 0.004838144 2495/2512     2
## R-HSA-2173782 42/10654 8.158747e-04 0.031411174 0.018035124 2495/2512     2
## R-HSA-432722  56/10654 1.447823e-03 0.039842592 0.022876129 2495/2512     2
## R-HSA-917937  58/10654 1.552309e-03 0.039842592 0.022876129 2495/2512     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_4"
##  [1] "ADH1B"  "ADIPOQ" "AGPAT2" "AOC3"   "CAV1"   "CEBPA"  "CIDEC"  "CRYAB" 
##  [9] "DEPP1"  "DGAT2"  "EMP1"   "FABP4"  "FASN"   "G0S2"   "GPAM"   "GPD1"  
## [17] "LIPE"   "LRP1"   "MCAM"   "MGLL"   "MT1X"   "PFKFB3" "PLIN1"  "PLIN4" 
## [25] "PNPLA2" "PTPRF"  "RASD1"  "RTN4"   "TRARG1"
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0008374 GO:0008374
## GO:0016747 GO:0016747
## GO:0004806 GO:0004806
## GO:0016411 GO:0016411
## GO:0016746 GO:0016746
## GO:0016616 GO:0016616
## GO:0016298 GO:0016298
## GO:0016614 GO:0016614
## GO:0052689 GO:0052689
## GO:0043394 GO:0043394
##                                                                                      Description
## GO:0008374                                                            O-acyltransferase activity
## GO:0016747           transferase activity, transferring acyl groups other than amino-acyl groups
## GO:0004806                                                          triglyceride lipase activity
## GO:0016411                                               acylglycerol O-acyltransferase activity
## GO:0016746                                        transferase activity, transferring acyl groups
## GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
## GO:0016298                                                                       lipase activity
## GO:0016614                              oxidoreductase activity, acting on CH-OH group of donors
## GO:0052689                                                   carboxylic ester hydrolase activity
## GO:0043394                                                                  proteoglycan binding
##            GeneRatio   BgRatio       pvalue    p.adjust      qvalue
## GO:0008374      3/25  47/17697 3.875695e-05 0.004340778 0.002774182
## GO:0016747      4/25 232/17697 2.932022e-04 0.010593125 0.006770042
## GO:0004806      2/25  21/17697 3.957735e-04 0.010593125 0.006770042
## GO:0016411      2/25  21/17697 3.957735e-04 0.010593125 0.006770042
## GO:0016746      4/25 264/17697 4.783924e-04 0.010593125 0.006770042
## GO:0016616      3/25 119/17697 6.120194e-04 0.010593125 0.006770042
## GO:0016298      3/25 127/17697 7.396059e-04 0.010593125 0.006770042
## GO:0016614      3/25 128/17697 7.566518e-04 0.010593125 0.006770042
## GO:0052689      3/25 136/17697 9.021019e-04 0.011226157 0.007174611
## GO:0043394      2/25  36/17697 1.172007e-03 0.013126480 0.008389104
##                            geneID Count
## GO:0008374      10555/84649/57678     3
## GO:0016747 10555/84649/2194/57678     4
## GO:0004806             3991/57104     2
## GO:0016411            10555/84649     2
## GO:0016746 10555/84649/2194/57678     4
## GO:0016616          125/2194/2819     3
## GO:0016298       3991/11343/57104     3
## GO:0016614          125/2194/2819     3
## GO:0052689       3991/11343/57104     3
## GO:0043394              4035/5792     2
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-8979227 R-HSA-8979227
## R-HSA-163560   R-HSA-163560
## R-HSA-1483206 R-HSA-1483206
## R-HSA-1483257 R-HSA-1483257
## R-HSA-381340   R-HSA-381340
## R-HSA-1483166 R-HSA-1483166
## R-HSA-75109     R-HSA-75109
## R-HSA-9006931 R-HSA-9006931
## R-HSA-2426168 R-HSA-2426168
## R-HSA-9024446 R-HSA-9024446
## R-HSA-1655829 R-HSA-1655829
##                                                                 Description
## R-HSA-8979227                                       Triglyceride metabolism
## R-HSA-163560                                        Triglyceride catabolism
## R-HSA-1483206                              Glycerophospholipid biosynthesis
## R-HSA-1483257                                       Phospholipid metabolism
## R-HSA-381340  Transcriptional regulation of white adipocyte differentiation
## R-HSA-1483166                                               Synthesis of PA
## R-HSA-75109                                       Triglyceride biosynthesis
## R-HSA-9006931                                Signaling by Nuclear Receptors
## R-HSA-2426168                Activation of gene expression by SREBF (SREBP)
## R-HSA-9024446                            NR1H2 and NR1H3-mediated signaling
## R-HSA-1655829       Regulation of cholesterol biosynthesis by SREBP (SREBF)
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-8979227      7/23  37/10654 7.863750e-13 5.740537e-11 3.807710e-11
## R-HSA-163560       5/23  24/10654 1.218406e-09 4.447182e-08 2.949825e-08
## R-HSA-1483206      6/23 129/10654 2.390810e-07 5.817638e-06 3.858852e-06
## R-HSA-1483257      6/23 212/10654 4.400125e-06 8.030228e-05 5.326467e-05
## R-HSA-381340       4/23  84/10654 2.840410e-05 4.146999e-04 2.750713e-04
## R-HSA-1483166      3/23  40/10654 8.242764e-05 1.002870e-03 6.652055e-04
## R-HSA-75109        2/23  13/10654 3.427525e-04 3.574418e-03 2.370919e-03
## R-HSA-9006931      4/23 299/10654 3.531139e-03 2.954235e-02 1.959550e-02
## R-HSA-2426168      2/23  42/10654 3.642207e-03 2.954235e-02 1.959550e-02
## R-HSA-9024446      2/23  47/10654 4.543001e-03 3.316391e-02 2.199769e-02
## R-HSA-1655829      2/23  55/10654 6.175833e-03 4.098508e-02 2.718549e-02
##                                             geneID Count
## R-HSA-8979227 857/84649/2167/57678/3991/11343/5346     7
## R-HSA-163560              857/2167/3991/11343/5346     5
## R-HSA-1483206   10555/84649/57678/2819/11343/57104     6
## R-HSA-1483257   10555/84649/57678/2819/11343/57104     6
## R-HSA-381340                   9370/1050/2167/5346     4
## R-HSA-1483166                     10555/57678/2819     3
## R-HSA-75109                            84649/57678     2
## R-HSA-9006931                  857/2194/57678/5346     4
## R-HSA-2426168                           2194/57678     2
## R-HSA-9024446                            2194/5346     2
## R-HSA-1655829                           2194/57678     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_5"
##  [1] "A2M"     "ADGRF5"  "ADGRL4"  "AQP1"    "B2M"     "BST2"    "BTNL9"  
##  [8] "CAVIN2"  "CD300LG" "CD74"    "CLDN5"   "COL4A1"  "EPAS1"   "GNG11"  
## [15] "HLA-A"   "HLA-B"   "HLA-C"   "HLA-E"   "IFI27"   "IGFBP4"  "IGFBP7" 
## [22] "MYH9"    "PECAM1"  "POSTN"   "RBP7"    "SPARCL1" "TCF4"    "THBS4"  
## [29] "TIMP3"   "TXNIP"   "UACA"    "VWF"    
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                                 Description GeneRatio
## GO:0042605 GO:0042605                     peptide antigen binding      4/32
## GO:0019838 GO:0019838                       growth factor binding      4/32
## GO:0042277 GO:0042277                             peptide binding      5/32
## GO:0003823 GO:0003823                             antigen binding      4/32
## GO:0005201 GO:0005201 extracellular matrix structural constituent      4/32
## GO:0008191 GO:0008191     metalloendopeptidase inhibitor activity      2/32
## GO:0033218 GO:0033218                               amide binding      5/32
## GO:0005520 GO:0005520          insulin-like growth factor binding      2/32
## GO:0002020 GO:0002020                            protease binding      3/32
## GO:0005178 GO:0005178                            integrin binding      3/32
## GO:0042287 GO:0042287                         MHC protein binding      2/32
## GO:0004866 GO:0004866            endopeptidase inhibitor activity      3/32
## GO:0030414 GO:0030414                peptidase inhibitor activity      3/32
## GO:0061135 GO:0061135            endopeptidase regulator activity      3/32
## GO:0004857 GO:0004857                   enzyme inhibitor activity      4/32
## GO:0005518 GO:0005518                            collagen binding      2/32
## GO:0061134 GO:0061134                peptidase regulator activity      3/32
##              BgRatio       pvalue     p.adjust       qvalue
## GO:0042605  31/17697 2.676416e-07 2.729944e-05 1.690368e-05
## GO:0019838 137/17697 1.044539e-04 4.161176e-03 2.576580e-03
## GO:0042277 295/17697 1.731991e-04 4.161176e-03 2.576580e-03
## GO:0003823 160/17697 1.899590e-04 4.161176e-03 2.576580e-03
## GO:0005201 163/17697 2.039792e-04 4.161176e-03 2.576580e-03
## GO:0008191  16/17697 3.741507e-04 6.010577e-03 3.721719e-03
## GO:0033218 356/17697 4.124906e-04 6.010577e-03 3.721719e-03
## GO:0005520  28/17697 1.162719e-03 1.482467e-02 9.179362e-03
## GO:0002020 128/17697 1.572633e-03 1.751886e-02 1.084759e-02
## GO:0005178 132/17697 1.717536e-03 1.751886e-02 1.084759e-02
## GO:0042287  40/17697 2.367023e-03 2.194876e-02 1.359056e-02
## GO:0004866 175/17697 3.818719e-03 3.035573e-02 1.879612e-02
## GO:0030414 182/17697 4.261807e-03 3.035573e-02 1.879612e-02
## GO:0061135 182/17697 4.261807e-03 3.035573e-02 1.879612e-02
## GO:0004857 375/17697 4.464079e-03 3.035573e-02 1.879612e-02
## GO:0005518  67/17697 6.508842e-03 4.149387e-02 2.569280e-02
## GO:0061134 219/17697 7.117461e-03 4.270477e-02 2.644258e-02
##                             geneID Count
## GO:0042605     3105/3106/3107/3133     4
## GO:0019838        2/1282/3487/3490     4
## GO:0042277 972/3105/3106/3107/3133     5
## GO:0003823     3105/3106/3107/3133     4
## GO:0005201    1282/3490/10631/7450     4
## GO:0008191                684/7078     2
## GO:0033218 972/3105/3106/3107/3133     5
## GO:0005520               3487/3490     2
## GO:0002020             2/7078/7450     3
## GO:0005178          4627/7060/7450     3
## GO:0042287                972/3133     2
## GO:0004866              2/684/7078     3
## GO:0030414              2/684/7078     3
## GO:0061135              2/684/7078     3
## GO:0004857        2/684/7078/10628     4
## GO:0005518               8404/7450     2
## GO:0061134              2/684/7078     3
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1236977 R-HSA-1236977
## R-HSA-983170   R-HSA-983170
## R-HSA-909733   R-HSA-909733
## R-HSA-913531   R-HSA-913531
## R-HSA-198933   R-HSA-198933
## R-HSA-1236974 R-HSA-1236974
## R-HSA-877300   R-HSA-877300
## R-HSA-1236975 R-HSA-1236975
## R-HSA-114608   R-HSA-114608
## R-HSA-76005     R-HSA-76005
## R-HSA-76002     R-HSA-76002
## R-HSA-216083   R-HSA-216083
## R-HSA-140837   R-HSA-140837
## R-HSA-983169   R-HSA-983169
## R-HSA-8957275 R-HSA-8957275
## R-HSA-2424491 R-HSA-2424491
## R-HSA-381426   R-HSA-381426
## R-HSA-140877   R-HSA-140877
## R-HSA-2172127 R-HSA-2172127
## R-HSA-432040   R-HSA-432040
##                                                                                                                               Description
## R-HSA-1236977                                                                                                  Endosomal/Vacuolar pathway
## R-HSA-983170                                                   Antigen Presentation: Folding, assembly and peptide loading of class I MHC
## R-HSA-909733                                                                                              Interferon alpha/beta signaling
## R-HSA-913531                                                                                                         Interferon Signaling
## R-HSA-198933                                                     Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-1236974                                                                                                        ER-Phagosome pathway
## R-HSA-877300                                                                                                   Interferon gamma signaling
## R-HSA-1236975                                                                                       Antigen processing-Cross presentation
## R-HSA-114608                                                                                                      Platelet degranulation 
## R-HSA-76005                                                                                  Response to elevated platelet cytosolic Ca2+
## R-HSA-76002                                                                                Platelet activation, signaling and aggregation
## R-HSA-216083                                                                                           Integrin cell surface interactions
## R-HSA-140837                                                                                   Intrinsic Pathway of Fibrin Clot Formation
## R-HSA-983169                                                                       Class I MHC mediated antigen processing & presentation
## R-HSA-8957275                                                                                  Post-translational protein phosphorylation
## R-HSA-2424491                                                                                                             DAP12 signaling
## R-HSA-381426  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
## R-HSA-140877                                                                                  Formation of Fibrin Clot (Clotting Cascade)
## R-HSA-2172127                                                                                                          DAP12 interactions
## R-HSA-432040                                                                 Vasopressin regulates renal water homeostasis via Aquaporins
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1236977      5/28  11/10654 3.930412e-11 6.406571e-09 4.716494e-09
## R-HSA-983170       5/28  25/10654 4.407362e-09 3.592000e-07 2.644417e-07
## R-HSA-909733       6/28  69/10654 1.991051e-08 1.081804e-06 7.964203e-07
## R-HSA-913531       7/28 199/10654 6.059964e-07 2.469435e-05 1.817989e-05
## R-HSA-198933       6/28 132/10654 9.720846e-07 3.168996e-05 2.333003e-05
## R-HSA-1236974      5/28  83/10654 2.169262e-06 5.893161e-05 4.338524e-05
## R-HSA-877300       5/28  92/10654 3.614972e-06 8.417720e-05 6.197095e-05
## R-HSA-1236975      5/28  99/10654 5.191562e-06 1.057781e-04 7.787344e-05
## R-HSA-114608       4/28 129/10654 3.352958e-04 6.072579e-03 4.470611e-03
## R-HSA-76005        4/28 134/10654 3.875588e-04 6.317208e-03 4.650705e-03
## R-HSA-76002        5/28 262/10654 5.350467e-04 7.928420e-03 5.836873e-03
## R-HSA-216083       3/28  85/10654 1.390180e-03 1.867523e-02 1.374863e-02
## R-HSA-140837       2/28  22/10654 1.489435e-03 1.867523e-02 1.374863e-02
## R-HSA-983169       5/28 371/10654 2.527845e-03 2.820501e-02 2.076443e-02
## R-HSA-8957275      3/28 108/10654 2.759841e-03 2.820501e-02 2.076443e-02
## R-HSA-2424491      2/28  30/10654 2.768590e-03 2.820501e-02 2.076443e-02
## R-HSA-381426       3/28 125/10654 4.169348e-03 3.997669e-02 2.943069e-02
## R-HSA-140877       2/28  39/10654 4.647825e-03 4.208863e-02 3.098550e-02
## R-HSA-2172127      2/28  43/10654 5.627364e-03 4.586301e-02 3.376418e-02
## R-HSA-432040       2/28  43/10654 5.627364e-03 4.586301e-02 3.376418e-02
##                                         geneID Count
## R-HSA-1236977          567/3105/3106/3107/3133     5
## R-HSA-983170           567/3105/3106/3107/3133     5
## R-HSA-909733      684/3105/3106/3107/3133/3429     6
## R-HSA-913531  567/684/3105/3106/3107/3133/3429     7
## R-HSA-198933    567/146894/3105/3106/3107/3133     6
## R-HSA-1236974          567/3105/3106/3107/3133     5
## R-HSA-877300           567/3105/3106/3107/3133     5
## R-HSA-1236975          567/3105/3106/3107/3133     5
## R-HSA-114608                  2/5175/7078/7450     4
## R-HSA-76005                   2/5175/7078/7450     4
## R-HSA-76002              2/2791/5175/7078/7450     5
## R-HSA-216083                    1282/5175/7450     3
## R-HSA-140837                            2/7450     2
## R-HSA-983169           567/3105/3106/3107/3133     5
## R-HSA-8957275                   3487/3490/8404     3
## R-HSA-2424491                         567/3133     2
## R-HSA-381426                    3487/3490/8404     3
## R-HSA-140877                            2/7450     2
## R-HSA-2172127                         567/3133     2
## R-HSA-432040                          358/2791     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_6"
##  [1] "CES1"  "DGAT2" "FTL"   "G0S2"  "GPD1"  "LEP"   "LPL"   "MGST1" "PLIN4"
## [10] "RBP4"  "SAA1"  "SAA2" 
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0004806 GO:0004806
## GO:0042056 GO:0042056
## GO:1901681 GO:1901681
## GO:0016298 GO:0016298
## GO:0048018 GO:0048018
## GO:0052689 GO:0052689
## GO:0008201 GO:0008201
## GO:0004322 GO:0004322
## GO:0016724 GO:0016724
## GO:0008199 GO:0008199
## GO:0043295 GO:0043295
## GO:1900750 GO:1900750
## GO:0043495 GO:0043495
## GO:0005539 GO:0005539
## GO:0019841 GO:0019841
## GO:0016918 GO:0016918
## GO:0043395 GO:0043395
## GO:0034185 GO:0034185
## GO:0016722 GO:0016722
## GO:0004602 GO:0004602
## GO:0016411 GO:0016411
## GO:0051428 GO:0051428
## GO:0008198 GO:0008198
## GO:0004364 GO:0004364
## GO:0090482 GO:0090482
## GO:0071813 GO:0071813
## GO:0071814 GO:0071814
## GO:0005501 GO:0005501
## GO:0019840 GO:0019840
## GO:0043394 GO:0043394
## GO:0019213 GO:0019213
## GO:1901618 GO:1901618
## GO:0008374 GO:0008374
##                                                                  Description
## GO:0004806                                      triglyceride lipase activity
## GO:0042056                                          chemoattractant activity
## GO:1901681                                           sulfur compound binding
## GO:0016298                                                   lipase activity
## GO:0048018                                          receptor ligand activity
## GO:0052689                               carboxylic ester hydrolase activity
## GO:0008201                                                   heparin binding
## GO:0004322                                              ferroxidase activity
## GO:0016724 oxidoreductase activity, oxidizing metal ions, oxygen as acceptor
## GO:0008199                                               ferric iron binding
## GO:0043295                                               glutathione binding
## GO:1900750                                              oligopeptide binding
## GO:0043495                                           protein membrane anchor
## GO:0005539                                         glycosaminoglycan binding
## GO:0019841                                                   retinol binding
## GO:0016918                                                   retinal binding
## GO:0043395                              heparan sulfate proteoglycan binding
## GO:0034185                                            apolipoprotein binding
## GO:0016722                     oxidoreductase activity, oxidizing metal ions
## GO:0004602                                   glutathione peroxidase activity
## GO:0016411                           acylglycerol O-acyltransferase activity
## GO:0051428                                  peptide hormone receptor binding
## GO:0008198                                              ferrous iron binding
## GO:0004364                                  glutathione transferase activity
## GO:0090482                        vitamin transmembrane transporter activity
## GO:0071813                                      lipoprotein particle binding
## GO:0071814                                     protein-lipid complex binding
## GO:0005501                                                  retinoid binding
## GO:0019840                                                isoprenoid binding
## GO:0043394                                              proteoglycan binding
## GO:0019213                                              deacetylase activity
## GO:1901618       organic hydroxy compound transmembrane transporter activity
## GO:0008374                                        O-acyltransferase activity
##            GeneRatio   BgRatio       pvalue    p.adjust      qvalue
## GO:0004806      2/11  21/17697 0.0000732890 0.003957606 0.001311487
## GO:0042056      2/11  38/17697 0.0002439332 0.006586198 0.002182561
## GO:1901681      3/11 250/17697 0.0004226375 0.007607475 0.002520996
## GO:0016298      2/11 127/17697 0.0026937169 0.027731119 0.009189650
## GO:0048018      3/11 482/17697 0.0028142626 0.027731119 0.009189650
## GO:0052689      2/11 136/17697 0.0030812354 0.027731119 0.009189650
## GO:0008201      2/11 169/17697 0.0047118149 0.031457027 0.010424356
## GO:0004322      1/11  10/17697 0.0061999579 0.031457027 0.010424356
## GO:0016724      1/11  10/17697 0.0061999579 0.031457027 0.010424356
## GO:0008199      1/11  11/17697 0.0068180277 0.031457027 0.010424356
## GO:0043295      1/11  11/17697 0.0068180277 0.031457027 0.010424356
## GO:1900750      1/11  12/17697 0.0074357480 0.031457027 0.010424356
## GO:0043495      1/11  13/17697 0.0080531191 0.031457027 0.010424356
## GO:0005539      2/11 229/17697 0.0084903741 0.031457027 0.010424356
## GO:0019841      1/11  15/17697 0.0092868140 0.031457027 0.010424356
## GO:0016918      1/11  16/17697 0.0099031382 0.031457027 0.010424356
## GO:0043395      1/11  16/17697 0.0099031382 0.031457027 0.010424356
## GO:0034185      1/11  17/17697 0.0105191138 0.031557342 0.010457599
## GO:0016722      1/11  19/17697 0.0117500201 0.031858857 0.010557516
## GO:0004602      1/11  21/17697 0.0129795342 0.031858857 0.010557516
## GO:0016411      1/11  21/17697 0.0129795342 0.031858857 0.010557516
## GO:0051428      1/11  21/17697 0.0129795342 0.031858857 0.010557516
## GO:0008198      1/11  24/17697 0.0148211981 0.034797595 0.011531367
## GO:0004364      1/11  27/17697 0.0166597375 0.035985033 0.011924865
## GO:0090482      1/11  27/17697 0.0166597375 0.035985033 0.011924865
## GO:0071813      1/11  33/17697 0.0203274619 0.039881982 0.013216251
## GO:0071814      1/11  33/17697 0.0203274619 0.039881982 0.013216251
## GO:0005501      1/11  35/17697 0.0215472703 0.039881982 0.013216251
## GO:0019840      1/11  36/17697 0.0221566565 0.039881982 0.013216251
## GO:0043394      1/11  36/17697 0.0221566565 0.039881982 0.013216251
## GO:0019213      1/11  44/17697 0.0270193397 0.045595136 0.015109499
## GO:1901618      1/11  44/17697 0.0270193397 0.045595136 0.015109499
## GO:0008374      1/11  47/17697 0.0288371709 0.047188098 0.015637381
##                    geneID Count
## GO:0004806      1066/4023     2
## GO:0042056      6288/6289     2
## GO:1901681 4023/4257/6288     3
## GO:0016298      1066/4023     2
## GO:0048018 3952/6288/6289     3
## GO:0052689      1066/4023     2
## GO:0008201      4023/6288     2
## GO:0004322           2512     1
## GO:0016724           2512     1
## GO:0008199           2512     1
## GO:0043295           4257     1
## GO:1900750           4257     1
## GO:0043495           4023     1
## GO:0005539      4023/6288     2
## GO:0019841           5950     1
## GO:0016918           5950     1
## GO:0043395           4023     1
## GO:0034185           4023     1
## GO:0016722           2512     1
## GO:0004602           4257     1
## GO:0016411          84649     1
## GO:0051428           3952     1
## GO:0008198           2512     1
## GO:0004364           4257     1
## GO:0090482           5950     1
## GO:0071813           4023     1
## GO:0071814           4023     1
## GO:0005501           5950     1
## GO:0019840           5950     1
## GO:0043394           4023     1
## GO:0019213           1066     1
## GO:1901618           5950     1
## GO:0008374          84649     1
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-2173782 R-HSA-2173782
## R-HSA-975634   R-HSA-975634
## R-HSA-6806667 R-HSA-6806667
## R-HSA-381340   R-HSA-381340
## R-HSA-2980736 R-HSA-2980736
## R-HSA-2187338 R-HSA-2187338
##                                                                 Description
## R-HSA-2173782          Binding and Uptake of Ligands by Scavenger Receptors
## R-HSA-975634                              Retinoid metabolism and transport
## R-HSA-6806667                            Metabolism of fat-soluble vitamins
## R-HSA-381340  Transcriptional regulation of white adipocyte differentiation
## R-HSA-2980736                                    Peptide hormone metabolism
## R-HSA-2187338                                      Visual phototransduction
##               GeneRatio   BgRatio       pvalue   p.adjust     qvalue    geneID
## R-HSA-2173782      2/10  42/10654 0.0006692059 0.01843814 0.01058649 2512/6288
## R-HSA-975634       2/10  43/10654 0.0007014985 0.01843814 0.01058649 4023/5950
## R-HSA-6806667      2/10  47/10654 0.0008380973 0.01843814 0.01058649 4023/5950
## R-HSA-381340       2/10  84/10654 0.0026530469 0.04011328 0.02303155 3952/4023
## R-HSA-2980736      2/10  90/10654 0.0030388851 0.04011328 0.02303155 1066/3952
## R-HSA-2187338      2/10 103/10654 0.0039599508 0.04355946 0.02501022 4023/5950
##               Count
## R-HSA-2173782     2
## R-HSA-975634      2
## R-HSA-6806667     2
## R-HSA-381340      2
## R-HSA-2980736     2
## R-HSA-2187338     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## Warning in clusterProfiler::bitr(d$gene_name, fromType = "SYMBOL", toType =
## "ENTREZID", : 2.27% of input gene IDs are fail to map...
## [1] "cluster_7"
##  [1] "AEBP1"    "APOD"     "C1R"      "C1S"      "C3"       "CCDC80"  
##  [7] "CFD"      "CFH"      "COL1A1"   "COL1A2"   "COL3A1"   "COL6A1"  
## [13] "COL6A2"   "COL6A3"   "CTSK"     "CXCL12"   "CXCL14"   "DCN"     
## [19] "FBLN1"    "FBLN2"    "GPC3"     "GPNMB"    "GPX3"     "GSN"     
## [25] "IFITM3"   "IGFBP3"   "IGFBP4"   "IGFBP6"   "LUM"      "MFAP4"   
## [31] "MGP"      "MMP2"     "MYOC"     "PDGFRA"   "PLPP3"    "S100A4"  
## [37] "S100A6"   "SERPING1" "SLIT3"    "SRPX"     "SVEP1"    "TIMP2"   
## [43] "TNXB"     "WISP2"   
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0005201 GO:0005201
## GO:0048407 GO:0048407
## GO:0001968 GO:0001968
## GO:0030020 GO:0030020
## GO:0019838 GO:0019838
## GO:0031994 GO:0031994
## GO:0061134 GO:0061134
## GO:0005178 GO:0005178
## GO:0005539 GO:0005539
## GO:0005518 GO:0005518
## GO:0005520 GO:0005520
## GO:0008201 GO:0008201
## GO:0030414 GO:0030414
## GO:0043394 GO:0043394
## GO:0002020 GO:0002020
## GO:1901681 GO:1901681
## GO:0004252 GO:0004252
## GO:0004866 GO:0004866
## GO:0008236 GO:0008236
## GO:0061135 GO:0061135
## GO:0017171 GO:0017171
## GO:0030021 GO:0030021
## GO:0004857 GO:0004857
## GO:0004175 GO:0004175
## GO:0001664 GO:0001664
## GO:0008009 GO:0008009
## GO:0050839 GO:0050839
## GO:0050840 GO:0050840
## GO:0048306 GO:0048306
## GO:0042379 GO:0042379
## GO:0017022 GO:0017022
## GO:0046332 GO:0046332
##                                                                              Description
## GO:0005201                                   extracellular matrix structural constituent
## GO:0048407                                        platelet-derived growth factor binding
## GO:0001968                                                           fibronectin binding
## GO:0030020       extracellular matrix structural constituent conferring tensile strength
## GO:0019838                                                         growth factor binding
## GO:0031994                                          insulin-like growth factor I binding
## GO:0061134                                                  peptidase regulator activity
## GO:0005178                                                              integrin binding
## GO:0005539                                                     glycosaminoglycan binding
## GO:0005518                                                              collagen binding
## GO:0005520                                            insulin-like growth factor binding
## GO:0008201                                                               heparin binding
## GO:0030414                                                  peptidase inhibitor activity
## GO:0043394                                                          proteoglycan binding
## GO:0002020                                                              protease binding
## GO:1901681                                                       sulfur compound binding
## GO:0004252                                            serine-type endopeptidase activity
## GO:0004866                                              endopeptidase inhibitor activity
## GO:0008236                                                serine-type peptidase activity
## GO:0061135                                              endopeptidase regulator activity
## GO:0017171                                                     serine hydrolase activity
## GO:0030021 extracellular matrix structural constituent conferring compression resistance
## GO:0004857                                                     enzyme inhibitor activity
## GO:0004175                                                        endopeptidase activity
## GO:0001664                                            G protein-coupled receptor binding
## GO:0008009                                                            chemokine activity
## GO:0050839                                                cell adhesion molecule binding
## GO:0050840                                                  extracellular matrix binding
## GO:0048306                                             calcium-dependent protein binding
## GO:0042379                                                    chemokine receptor binding
## GO:0017022                                                                myosin binding
## GO:0046332                                                                  SMAD binding
##            GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## GO:0005201     15/43 163/17697 1.832871e-20 1.649584e-18 8.296154e-19
## GO:0048407      5/43  11/17697 3.043317e-11 1.223042e-09 6.150973e-10
## GO:0001968      6/43  27/17697 4.076808e-11 1.223042e-09 6.150973e-10
## GO:0030020      6/43  41/17697 6.038994e-10 1.358774e-08 6.833598e-09
## GO:0019838      8/43 137/17697 1.211771e-09 2.181189e-08 1.096972e-08
## GO:0031994      3/43  12/17697 2.895130e-06 4.342695e-05 2.184045e-05
## GO:0061134      6/43 219/17697 1.394903e-05 1.793447e-04 9.019676e-05
## GO:0005178      5/43 132/17697 1.640569e-05 1.796401e-04 9.034534e-05
## GO:0005539      6/43 229/17697 1.796401e-05 1.796401e-04 9.034534e-05
## GO:0005518      4/43  67/17697 2.071866e-05 1.864679e-04 9.377919e-05
## GO:0005520      3/43  28/17697 4.195765e-05 3.432899e-04 1.726487e-04
## GO:0008201      5/43 169/17697 5.372092e-05 4.029069e-04 2.026316e-04
## GO:0030414      5/43 182/17697 7.635348e-05 5.286010e-04 2.658461e-04
## GO:0043394      3/43  36/17697 9.021554e-05 5.799570e-04 2.916743e-04
## GO:0002020      4/43 128/17697 2.590064e-04 1.554038e-03 7.815632e-04
## GO:1901681      5/43 250/17697 3.356712e-04 1.888150e-03 9.495961e-04
## GO:0004252      4/43 160/17697 6.034795e-04 3.194891e-03 1.606787e-03
## GO:0004866      4/43 175/17697 8.439349e-04 4.219675e-03 2.122176e-03
## GO:0008236      4/43 182/17697 9.765292e-04 4.394381e-03 2.210040e-03
## GO:0061135      4/43 182/17697 9.765292e-04 4.394381e-03 2.210040e-03
## GO:0017171      4/43 186/17697 1.058556e-03 4.536670e-03 2.281600e-03
## GO:0030021      2/43  22/17697 1.291656e-03 5.284048e-03 2.657474e-03
## GO:0004857      5/43 375/17697 2.066238e-03 8.085280e-03 4.066281e-03
## GO:0004175      5/43 427/17697 3.616286e-03 1.356107e-02 6.820188e-03
## GO:0001664      4/43 280/17697 4.661366e-03 1.678092e-02 8.439526e-03
## GO:0008009      2/43  49/17697 6.308217e-03 2.183614e-02 1.098192e-02
## GO:0050839      5/43 499/17697 6.955493e-03 2.318498e-02 1.166028e-02
## GO:0050840      2/43  57/17697 8.456738e-03 2.718237e-02 1.367067e-02
## GO:0048306      2/43  61/17697 9.637379e-03 2.990911e-02 1.504201e-02
## GO:0042379      2/43  66/17697 1.121011e-02 3.363033e-02 1.691350e-02
## GO:0017022      2/43  71/17697 1.288802e-02 3.741684e-02 1.881782e-02
## GO:0046332      2/43  80/17697 1.616489e-02 4.546376e-02 2.286481e-02
##                                                                               geneID
## GO:0005201 165/1277/1278/1281/1291/1292/1293/1634/2192/2199/4060/4239/4256/8406/7148
## GO:0048407                                                  1277/1278/1281/1291/5156
## GO:0001968                                           151887/1513/2192/3486/3489/4653
## GO:0030020                                             1277/1278/1281/1291/1292/1293
## GO:0019838                                   1277/1278/1281/1291/3486/3487/3489/5156
## GO:0031994                                                            3486/3487/3489
## GO:0061134                                               718/1293/2192/2719/710/7077
## GO:0005178                                                 1281/6387/10457/7077/7148
## GO:0005539                                          151887/3075/1634/10457/6586/7148
## GO:0005518                                                        165/1513/1634/4060
## GO:0005520                                                            3486/3487/3489
## GO:0008201                                               151887/3075/10457/6586/7148
## GO:0030414                                                    718/1293/2719/710/7077
## GO:0043394                                                           3075/1513/10457
## GO:0002020                                                       1277/1278/1281/7077
## GO:1901681                                               151887/3075/10457/6586/7148
## GO:0004252                                                         715/716/1675/4313
## GO:0004866                                                         718/1293/710/7077
## GO:0008236                                                         715/716/1675/4313
## GO:0061135                                                         718/1293/710/7077
## GO:0017171                                                         715/716/1675/4313
## GO:0030021                                                                 1634/4060
## GO:0004857                                                    718/1293/2719/710/7077
## GO:0004175                                                    715/716/1675/1513/4313
## GO:0001664                                                        718/6387/9547/4653
## GO:0008009                                                                 6387/9547
## GO:0050839                                                 1281/6387/10457/7077/7148
## GO:0050840                                                                 1634/2199
## GO:0048306                                                                 6275/6277
## GO:0042379                                                                 6387/9547
## GO:0017022                                                                 2934/4653
## GO:0046332                                                                 1278/1281
##            Count
## GO:0005201    15
## GO:0048407     5
## GO:0001968     6
## GO:0030020     6
## GO:0019838     8
## GO:0031994     3
## GO:0061134     6
## GO:0005178     5
## GO:0005539     6
## GO:0005518     4
## GO:0005520     3
## GO:0008201     5
## GO:0030414     5
## GO:0043394     3
## GO:0002020     4
## GO:1901681     5
## GO:0004252     4
## GO:0004866     4
## GO:0008236     4
## GO:0061135     4
## GO:0017171     4
## GO:0030021     2
## GO:0004857     5
## GO:0004175     5
## GO:0001664     4
## GO:0008009     2
## GO:0050839     5
## GO:0050840     2
## GO:0048306     2
## GO:0042379     2
## GO:0017022     2
## GO:0046332     2
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1474244 R-HSA-1474244
## R-HSA-3000178 R-HSA-3000178
## R-HSA-1474228 R-HSA-1474228
## R-HSA-1442490 R-HSA-1442490
## R-HSA-8948216 R-HSA-8948216
## R-HSA-216083   R-HSA-216083
## R-HSA-166658   R-HSA-166658
## R-HSA-2022090 R-HSA-2022090
## R-HSA-1650814 R-HSA-1650814
## R-HSA-977606   R-HSA-977606
## R-HSA-1474290 R-HSA-1474290
## R-HSA-166663   R-HSA-166663
## R-HSA-186797   R-HSA-186797
## R-HSA-381426   R-HSA-381426
## R-HSA-419037   R-HSA-419037
## R-HSA-3000480 R-HSA-3000480
## R-HSA-375165   R-HSA-375165
## R-HSA-3000170 R-HSA-3000170
## R-HSA-9006934 R-HSA-9006934
## R-HSA-8874081 R-HSA-8874081
## R-HSA-1592389 R-HSA-1592389
## R-HSA-2129379 R-HSA-2129379
## R-HSA-3560782 R-HSA-3560782
## R-HSA-8875878 R-HSA-8875878
## R-HSA-2173782 R-HSA-2173782
## R-HSA-8957275 R-HSA-8957275
## R-HSA-1566948 R-HSA-1566948
## R-HSA-430116   R-HSA-430116
## R-HSA-198933   R-HSA-198933
## R-HSA-3000171 R-HSA-3000171
## R-HSA-166786   R-HSA-166786
## R-HSA-2214320 R-HSA-2214320
## R-HSA-75892     R-HSA-75892
## R-HSA-2243919 R-HSA-2243919
## R-HSA-3560783 R-HSA-3560783
## R-HSA-3560801 R-HSA-3560801
## R-HSA-4420332 R-HSA-4420332
## R-HSA-6806834 R-HSA-6806834
## R-HSA-1971475 R-HSA-1971475
## R-HSA-114604   R-HSA-114604
## R-HSA-76009     R-HSA-76009
## R-HSA-1630316 R-HSA-1630316
## R-HSA-76002     R-HSA-76002
## R-HSA-3781865 R-HSA-3781865
## R-HSA-1793185 R-HSA-1793185
## R-HSA-1638091 R-HSA-1638091
##                                                                                                                               Description
## R-HSA-1474244                                                                                           Extracellular matrix organization
## R-HSA-3000178                                                                                                           ECM proteoglycans
## R-HSA-1474228                                                                                     Degradation of the extracellular matrix
## R-HSA-1442490                                                                                                        Collagen degradation
## R-HSA-8948216                                                                                                Collagen chain trimerization
## R-HSA-216083                                                                                           Integrin cell surface interactions
## R-HSA-166658                                                                                                           Complement cascade
## R-HSA-2022090                                                                Assembly of collagen fibrils and other multimeric structures
## R-HSA-1650814                                                                                 Collagen biosynthesis and modifying enzymes
## R-HSA-977606                                                                                             Regulation of Complement cascade
## R-HSA-1474290                                                                                                          Collagen formation
## R-HSA-166663                                                                                             Initial triggering of complement
## R-HSA-186797                                                                                                            Signaling by PDGF
## R-HSA-381426  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
## R-HSA-419037                                                                                                           NCAM1 interactions
## R-HSA-3000480                                                                                             Scavenging by Class A Receptors
## R-HSA-375165                                                                                        NCAM signaling for neurite out-growth
## R-HSA-3000170                                                                                                       Syndecan interactions
## R-HSA-9006934                                                                                      Signaling by Receptor Tyrosine Kinases
## R-HSA-8874081                                                                                                MET activates PTK2 signaling
## R-HSA-1592389                                                                                     Activation of Matrix Metalloproteinases
## R-HSA-2129379                                                                                    Molecules associated with elastic fibres
## R-HSA-3560782                                                                       Diseases associated with glycosaminoglycan metabolism
## R-HSA-8875878                                                                                                  MET promotes cell motility
## R-HSA-2173782                                                                        Binding and Uptake of Ligands by Scavenger Receptors
## R-HSA-8957275                                                                                  Post-translational protein phosphorylation
## R-HSA-1566948                                                                                                     Elastic fibre formation
## R-HSA-430116                                                                                              GP1b-IX-V activation signalling
## R-HSA-198933                                                     Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-3000171                                                                                      Non-integrin membrane-ECM interactions
## R-HSA-166786                                                                                             Creation of C4 and C2 activators
## R-HSA-2214320                                                                                                  Anchoring fibril formation
## R-HSA-75892                                                                                         Platelet Adhesion to exposed collagen
## R-HSA-2243919                                                                                            Crosslinking of collagen fibrils
## R-HSA-3560783                                                                                Defective B4GALT7 causes EDS, progeroid type
## R-HSA-3560801                                                                                             Defective B3GAT3 causes JDSSDHD
## R-HSA-4420332                                                                                  Defective B3GALT6 causes EDSP2 and SEMDJL1
## R-HSA-6806834                                                                                                            Signaling by MET
## R-HSA-1971475                                                             A tetrasaccharide linker sequence is required for GAG synthesis
## R-HSA-114604                                                                                             GPVI-mediated activation cascade
## R-HSA-76009                                                                                         Platelet Aggregation (Plug Formation)
## R-HSA-1630316                                                                                                Glycosaminoglycan metabolism
## R-HSA-76002                                                                                Platelet activation, signaling and aggregation
## R-HSA-3781865                                                                                                   Diseases of glycosylation
## R-HSA-1793185                                                                             Chondroitin sulfate/dermatan sulfate metabolism
## R-HSA-1638091                                                                                 Heparan sulfate/heparin (HS-GAG) metabolism
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1474244     15/34 301/10654 4.721437e-15 5.949011e-13 3.478954e-13
## R-HSA-3000178      9/34  76/10654 1.334713e-12 8.408689e-11 4.917362e-11
## R-HSA-1474228     10/34 140/10654 1.112901e-11 4.674184e-10 2.733441e-10
## R-HSA-1442490      8/34  64/10654 1.732511e-11 5.457410e-10 3.191468e-10
## R-HSA-8948216      6/34  44/10654 4.295783e-09 1.082537e-07 6.330628e-08
## R-HSA-216083       7/34  85/10654 7.234732e-09 1.519294e-07 8.884759e-08
## R-HSA-166658       6/34  58/10654 2.386414e-08 4.295546e-07 2.512015e-07
## R-HSA-2022090      6/34  61/10654 3.251631e-08 5.121319e-07 2.994924e-07
## R-HSA-1650814      6/34  67/10654 5.765409e-08 8.071573e-07 4.720218e-07
## R-HSA-977606       5/34  47/10654 3.394877e-07 3.911295e-06 2.287307e-06
## R-HSA-1474290      6/34  90/10654 3.414622e-07 3.911295e-06 2.287307e-06
## R-HSA-166663       4/34  23/10654 7.332862e-07 7.699506e-06 4.502635e-06
## R-HSA-186797       5/34  58/10654 9.890561e-07 9.586236e-06 5.605986e-06
## R-HSA-381426       6/34 125/10654 2.376501e-06 2.138851e-05 1.250790e-05
## R-HSA-419037       4/34  42/10654 8.880229e-06 7.459392e-05 4.362218e-05
## R-HSA-3000480      3/34  19/10654 2.778907e-05 2.188390e-04 1.279760e-04
## R-HSA-375165       4/34  63/10654 4.507352e-05 3.340743e-04 1.953651e-04
## R-HSA-3000170      3/34  27/10654 8.243173e-05 5.770221e-04 3.374398e-04
## R-HSA-9006934      8/34 473/10654 9.301072e-05 6.168079e-04 3.607064e-04
## R-HSA-8874081      3/34  30/10654 1.136717e-04 7.161320e-04 4.187906e-04
## R-HSA-1592389      3/34  33/10654 1.517608e-04 9.105645e-04 5.324939e-04
## R-HSA-2129379      3/34  38/10654 2.321066e-04 1.329338e-03 7.773904e-04
## R-HSA-3560782      3/34  41/10654 2.913858e-04 1.529775e-03 8.946055e-04
## R-HSA-8875878      3/34  41/10654 2.913858e-04 1.529775e-03 8.946055e-04
## R-HSA-2173782      3/34  42/10654 3.131170e-04 1.578110e-03 9.228711e-04
## R-HSA-8957275      4/34 108/10654 3.664270e-04 1.775762e-03 1.038457e-03
## R-HSA-1566948      3/34  45/10654 3.845106e-04 1.794383e-03 1.049347e-03
## R-HSA-430116       2/34  12/10654 6.395179e-04 2.877831e-03 1.682942e-03
## R-HSA-198933       4/34 132/10654 7.827131e-04 3.400753e-03 1.988745e-03
## R-HSA-3000171      3/34  59/10654 8.544569e-04 3.569612e-03 2.087492e-03
## R-HSA-166786       2/34  14/10654 8.782379e-04 3.569612e-03 2.087492e-03
## R-HSA-2214320      2/34  15/10654 1.011326e-03 3.861428e-03 2.258145e-03
## R-HSA-75892        2/34  15/10654 1.011326e-03 3.861428e-03 2.258145e-03
## R-HSA-2243919      2/34  18/10654 1.464833e-03 5.428499e-03 3.174561e-03
## R-HSA-3560783      2/34  20/10654 1.811816e-03 6.169970e-03 3.608169e-03
## R-HSA-3560801      2/34  20/10654 1.811816e-03 6.169970e-03 3.608169e-03
## R-HSA-4420332      2/34  20/10654 1.811816e-03 6.169970e-03 3.608169e-03
## R-HSA-6806834      3/34  79/10654 1.990029e-03 6.598517e-03 3.858782e-03
## R-HSA-1971475      2/34  26/10654 3.062242e-03 9.893398e-03 5.785613e-03
## R-HSA-114604       2/34  35/10654 5.506522e-03 1.734555e-02 1.014359e-02
## R-HSA-76009        2/34  39/10654 6.803276e-03 2.090763e-02 1.222668e-02
## R-HSA-1630316      3/34 124/10654 7.078589e-03 2.123577e-02 1.241858e-02
## R-HSA-76002        4/34 262/10654 9.281933e-03 2.719822e-02 1.590539e-02
## R-HSA-3781865      3/34 143/10654 1.045335e-02 2.993458e-02 1.750560e-02
## R-HSA-1793185      2/34  50/10654 1.100355e-02 3.080994e-02 1.801751e-02
## R-HSA-1638091      2/34  55/10654 1.320718e-02 3.617620e-02 2.115567e-02
##                                                                                   geneID
## R-HSA-1474244 1277/1278/1281/1291/1292/1293/1513/1634/2192/2199/4060/4239/4313/7077/7148
## R-HSA-3000178                               1277/1278/1281/1291/1292/1293/1634/4060/7148
## R-HSA-1474228                          1277/1278/1281/1291/1292/1293/1513/1634/4313/7077
## R-HSA-1442490                                    1277/1278/1281/1291/1292/1293/1513/4313
## R-HSA-8948216                                              1277/1278/1281/1291/1292/1293
## R-HSA-216083                                          1277/1278/1281/1291/1292/1293/4060
## R-HSA-166658                                                   715/716/718/1675/3075/710
## R-HSA-2022090                                              1277/1278/1281/1291/1292/1293
## R-HSA-1650814                                              1277/1278/1281/1291/1292/1293
## R-HSA-977606                                                        715/716/718/3075/710
## R-HSA-1474290                                              1277/1278/1281/1291/1292/1293
## R-HSA-166663                                                            715/716/718/1675
## R-HSA-186797                                                    1281/1291/1292/1293/5156
## R-HSA-381426                                                718/2719/3486/3487/3489/4313
## R-HSA-419037                                                         1281/1291/1292/1293
## R-HSA-3000480                                                             1277/1278/1281
## R-HSA-375165                                                         1281/1291/1292/1293
## R-HSA-3000170                                                             1277/1278/1281
## R-HSA-9006934                                    1277/1278/1281/1291/1292/1293/6387/5156
## R-HSA-8874081                                                             1277/1278/1281
## R-HSA-1592389                                                             1513/4313/7077
## R-HSA-2129379                                                             2192/2199/4239
## R-HSA-3560782                                                             1634/2719/4060
## R-HSA-8875878                                                             1277/1278/1281
## R-HSA-2173782                                                             1277/1278/1281
## R-HSA-8957275                                                         718/2719/3486/3487
## R-HSA-1566948                                                             2192/2199/4239
## R-HSA-430116                                                                   1277/1278
## R-HSA-198933                                                          718/1277/1278/1281
## R-HSA-3000171                                                             1277/1278/1281
## R-HSA-166786                                                                     715/716
## R-HSA-2214320                                                                  1277/1278
## R-HSA-75892                                                                    1277/1278
## R-HSA-2243919                                                                  1277/1278
## R-HSA-3560783                                                                  1634/2719
## R-HSA-3560801                                                                  1634/2719
## R-HSA-4420332                                                                  1634/2719
## R-HSA-6806834                                                             1277/1278/1281
## R-HSA-1971475                                                                  1634/2719
## R-HSA-114604                                                                   1277/1278
## R-HSA-76009                                                                    1277/1278
## R-HSA-1630316                                                             1634/2719/4060
## R-HSA-76002                                                           1675/1277/1278/710
## R-HSA-3781865                                                             1634/2719/4060
## R-HSA-1793185                                                                  1634/2719
## R-HSA-1638091                                                                  1634/2719
##               Count
## R-HSA-1474244    15
## R-HSA-3000178     9
## R-HSA-1474228    10
## R-HSA-1442490     8
## R-HSA-8948216     6
## R-HSA-216083      7
## R-HSA-166658      6
## R-HSA-2022090     6
## R-HSA-1650814     6
## R-HSA-977606      5
## R-HSA-1474290     6
## R-HSA-166663      4
## R-HSA-186797      5
## R-HSA-381426      6
## R-HSA-419037      4
## R-HSA-3000480     3
## R-HSA-375165      4
## R-HSA-3000170     3
## R-HSA-9006934     8
## R-HSA-8874081     3
## R-HSA-1592389     3
## R-HSA-2129379     3
## R-HSA-3560782     3
## R-HSA-8875878     3
## R-HSA-2173782     3
## R-HSA-8957275     4
## R-HSA-1566948     3
## R-HSA-430116      2
## R-HSA-198933      4
## R-HSA-3000171     3
## R-HSA-166786      2
## R-HSA-2214320     2
## R-HSA-75892       2
## R-HSA-2243919     2
## R-HSA-3560783     2
## R-HSA-3560801     2
## R-HSA-4420332     2
## R-HSA-6806834     3
## R-HSA-1971475     2
## R-HSA-114604      2
## R-HSA-76009       2
## R-HSA-1630316     3
## R-HSA-76002       4
## R-HSA-3781865     3
## R-HSA-1793185     2
## R-HSA-1638091     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_8"
##  [1] "A2M"     "AIF1"    "B2M"     "C1QA"    "C1QB"    "C1QC"    "CD14"   
##  [8] "CD163"   "CD74"    "CSF1R"   "CST3"    "CTSB"    "CTSC"    "CTSD"   
## [15] "DAB2"    "F13A1"   "FAU"     "FCGR2B"  "FCGRT"   "FOLR2"   "FTL"    
## [22] "GRN"     "HLA-A"   "HLA-B"   "HLA-DRA" "HLA-E"   "LGMN"    "LYVE1"  
## [29] "MAF"     "MAFB"    "MARCO"   "MPEG1"   "MRC1"    "MS4A4A"  "MS4A6A" 
## [36] "NPC2"    "PLTP"    "PSAP"    "RNASE1"  "SELENOP" "SLC40A1" "STAB1"  
## [43] "TMSB10"  "TMSB4X"  "TPT1"    "TYROBP" 
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                                     Description GeneRatio
## GO:0033218 GO:0033218                                   amide binding     14/44
## GO:0042277 GO:0042277                                 peptide binding     11/44
## GO:0038024 GO:0038024                         cargo receptor activity      6/44
## GO:0042605 GO:0042605                         peptide antigen binding      4/44
## GO:0001540 GO:0001540                            amyloid-beta binding      5/44
## GO:0005044 GO:0005044                     scavenger receptor activity      3/44
## GO:0019864 GO:0019864                                     IgG binding      2/44
## GO:0097001 GO:0097001                                ceramide binding      2/44
## GO:0003823 GO:0003823                                 antigen binding      4/44
## GO:0023026 GO:0023026            MHC class II protein complex binding      2/44
## GO:0008329 GO:0008329 signaling pattern recognition receptor activity      2/44
## GO:0005540 GO:0005540                         hyaluronic acid binding      2/44
## GO:0038187 GO:0038187           pattern recognition receptor activity      2/44
## GO:0031406 GO:0031406                         carboxylic acid binding      4/44
## GO:0046625 GO:0046625                            sphingolipid binding      2/44
## GO:0019865 GO:0019865                          immunoglobulin binding      2/44
## GO:0120013 GO:0120013           intermembrane lipid transfer activity      2/44
## GO:0043177 GO:0043177                            organic acid binding      4/44
## GO:0023023 GO:0023023                     MHC protein complex binding      2/44
## GO:0003785 GO:0003785                           actin monomer binding      2/44
## GO:0004197 GO:0004197            cysteine-type endopeptidase activity      3/44
## GO:0002020 GO:0002020                                protease binding      3/44
## GO:0019955 GO:0019955                                cytokine binding      3/44
## GO:0042287 GO:0042287                             MHC protein binding      2/44
##              BgRatio       pvalue     p.adjust       qvalue
## GO:0033218 356/17697 9.179048e-14 1.275888e-11 8.019589e-12
## GO:0042277 295/17697 1.078862e-10 7.498094e-09 4.712925e-09
## GO:0038024  85/17697 6.260799e-08 2.900837e-06 1.823320e-06
## GO:0042605  31/17697 9.956612e-07 3.459923e-05 2.174734e-05
## GO:0001540  78/17697 1.386723e-06 3.855090e-05 2.423116e-05
## GO:0005044  51/17697 2.747463e-04 6.364956e-03 4.000692e-03
## GO:0019864  11/17697 3.275843e-04 6.504889e-03 4.088646e-03
## GO:0097001  14/17697 5.394383e-04 9.372740e-03 5.891234e-03
## GO:0003823 160/17697 6.591923e-04 9.856520e-03 6.195313e-03
## GO:0023026  16/17697 7.091021e-04 9.856520e-03 6.195313e-03
## GO:0008329  20/17697 1.115673e-03 1.275668e-02 8.018208e-03
## GO:0005540  21/17697 1.231166e-03 1.275668e-02 8.018208e-03
## GO:0038187  21/17697 1.231166e-03 1.275668e-02 8.018208e-03
## GO:0031406 193/17697 1.323682e-03 1.275668e-02 8.018208e-03
## GO:0046625  23/17697 1.478586e-03 1.275668e-02 8.018208e-03
## GO:0019865  24/17697 1.610459e-03 1.275668e-02 8.018208e-03
## GO:0120013  24/17697 1.610459e-03 1.275668e-02 8.018208e-03
## GO:0043177 205/17697 1.651944e-03 1.275668e-02 8.018208e-03
## GO:0023023  25/17697 1.747738e-03 1.278609e-02 8.036692e-03
## GO:0003785  28/17697 2.191752e-03 1.523268e-02 9.574497e-03
## GO:0004197 116/17697 2.988440e-03 1.978063e-02 1.243311e-02
## GO:0002020 128/17697 3.942609e-03 2.382707e-02 1.497650e-02
## GO:0019955 128/17697 3.942609e-03 2.382707e-02 1.497650e-02
## GO:0042287  40/17697 4.437947e-03 2.570311e-02 1.615568e-02
##                                                                         geneID
## GO:0033218 712/929/972/1471/2213/2350/3105/3106/3122/3133/8685/5360/5660/30061
## GO:0042277                712/929/972/1471/2213/3105/3106/3122/3133/8685/30061
## GO:0038024                                      9332/1601/2350/8685/4360/23166
## GO:0042605                                                 3105/3106/3122/3133
## GO:0001540                                              712/972/1471/2213/8685
## GO:0005044                                                     9332/8685/23166
## GO:0019864                                                           2213/2217
## GO:0097001                                                           5360/5660
## GO:0003823                                                 3105/3106/3122/3133
## GO:0023026                                                            972/3122
## GO:0008329                                                            929/8685
## GO:0005540                                                         10894/23166
## GO:0038187                                                            929/8685
## GO:0031406                                               2350/10894/5660/23166
## GO:0046625                                                           5360/5660
## GO:0019865                                                           2213/2217
## GO:0120013                                                          10577/5360
## GO:0043177                                               2350/10894/5660/23166
## GO:0023023                                                            972/3122
## GO:0003785                                                           9168/7114
## GO:0004197                                                      1508/1075/5641
## GO:0002020                                                         2/1471/5660
## GO:0019955                                                          2/972/1436
## GO:0042287                                                            972/3133
##            Count
## GO:0033218    14
## GO:0042277    11
## GO:0038024     6
## GO:0042605     4
## GO:0001540     5
## GO:0005044     3
## GO:0019864     2
## GO:0097001     2
## GO:0003823     4
## GO:0023026     2
## GO:0008329     2
## GO:0005540     2
## GO:0038187     2
## GO:0031406     4
## GO:0046625     2
## GO:0019865     2
## GO:0120013     2
## GO:0043177     4
## GO:0023023     2
## GO:0003785     2
## GO:0004197     3
## GO:0002020     3
## GO:0019955     3
## GO:0042287     2
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1236977 R-HSA-1236977
## R-HSA-6798695 R-HSA-6798695
## R-HSA-1236975 R-HSA-1236975
## R-HSA-983170   R-HSA-983170
## R-HSA-2132295 R-HSA-2132295
## R-HSA-198933   R-HSA-198933
## R-HSA-1236974 R-HSA-1236974
## R-HSA-2173782 R-HSA-2173782
## R-HSA-166786   R-HSA-166786
## R-HSA-877300   R-HSA-877300
## R-HSA-166663   R-HSA-166663
## R-HSA-114608   R-HSA-114608
## R-HSA-76005     R-HSA-76005
## R-HSA-2424491 R-HSA-2424491
## R-HSA-2172127 R-HSA-2172127
## R-HSA-977606   R-HSA-977606
## R-HSA-913531   R-HSA-913531
## R-HSA-1679131 R-HSA-1679131
## R-HSA-166658   R-HSA-166658
## R-HSA-983169   R-HSA-983169
## R-HSA-174824   R-HSA-174824
## R-HSA-909733   R-HSA-909733
## R-HSA-3000480 R-HSA-3000480
## R-HSA-76002     R-HSA-76002
## R-HSA-140877   R-HSA-140877
##                                                                              Description
## R-HSA-1236977                                                 Endosomal/Vacuolar pathway
## R-HSA-6798695                                                   Neutrophil degranulation
## R-HSA-1236975                                      Antigen processing-Cross presentation
## R-HSA-983170  Antigen Presentation: Folding, assembly and peptide loading of class I MHC
## R-HSA-2132295                                          MHC class II antigen presentation
## R-HSA-198933    Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-1236974                                                       ER-Phagosome pathway
## R-HSA-2173782                       Binding and Uptake of Ligands by Scavenger Receptors
## R-HSA-166786                                            Creation of C4 and C2 activators
## R-HSA-877300                                                  Interferon gamma signaling
## R-HSA-166663                                            Initial triggering of complement
## R-HSA-114608                                                     Platelet degranulation 
## R-HSA-76005                                 Response to elevated platelet cytosolic Ca2+
## R-HSA-2424491                                                            DAP12 signaling
## R-HSA-2172127                                                         DAP12 interactions
## R-HSA-977606                                            Regulation of Complement cascade
## R-HSA-913531                                                        Interferon Signaling
## R-HSA-1679131                                Trafficking and processing of endosomal TLR
## R-HSA-166658                                                          Complement cascade
## R-HSA-983169                      Class I MHC mediated antigen processing & presentation
## R-HSA-174824                      Plasma lipoprotein assembly, remodeling, and clearance
## R-HSA-909733                                             Interferon alpha/beta signaling
## R-HSA-3000480                                            Scavenging by Class A Receptors
## R-HSA-76002                               Platelet activation, signaling and aggregation
## R-HSA-140877                                 Formation of Fibrin Clot (Clotting Cascade)
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1236977      4/38  11/10654 4.459540e-08 4.019555e-06 3.098841e-06
## R-HSA-6798695     12/38 480/10654 5.661345e-08 4.019555e-06 3.098841e-06
## R-HSA-1236975      6/38  99/10654 1.199505e-06 5.677655e-05 4.377140e-05
## R-HSA-983170       4/38  25/10654 1.649394e-06 5.855348e-05 4.514130e-05
## R-HSA-2132295      6/38 123/10654 4.275123e-06 1.214135e-04 9.360270e-05
## R-HSA-198933       6/38 132/10654 6.435270e-06 1.523014e-04 1.174155e-04
## R-HSA-1236974      5/38  83/10654 1.042276e-05 2.114332e-04 1.630026e-04
## R-HSA-2173782      4/38  42/10654 1.397386e-05 2.340110e-04 1.804088e-04
## R-HSA-166786       3/38  14/10654 1.483168e-05 2.340110e-04 1.804088e-04
## R-HSA-877300       5/38  92/10654 1.724738e-05 2.449128e-04 1.888134e-04
## R-HSA-166663       3/38  23/10654 7.057904e-05 9.111113e-04 7.024134e-04
## R-HSA-114608       5/38 129/10654 8.771981e-05 1.038018e-03 8.002509e-04
## R-HSA-76005        5/38 134/10654 1.050369e-04 1.147326e-03 8.845212e-04
## R-HSA-2424491      3/38  30/10654 1.590367e-04 1.613086e-03 1.243595e-03
## R-HSA-2172127      3/38  43/10654 4.682010e-04 4.432303e-03 3.417046e-03
## R-HSA-977606       3/38  47/10654 6.091563e-04 5.406262e-03 4.167912e-03
## R-HSA-913531       5/38 199/10654 6.574446e-04 5.491596e-03 4.233699e-03
## R-HSA-1679131      2/38  13/10654 9.426078e-04 7.436128e-03 5.732819e-03
## R-HSA-166658       3/38  58/10654 1.128280e-03 8.432409e-03 6.500894e-03
## R-HSA-983169       6/38 371/10654 1.838797e-03 1.203657e-02 9.279489e-03
## R-HSA-174824       3/38  69/10654 1.864820e-03 1.203657e-02 9.279489e-03
## R-HSA-909733       3/38  69/10654 1.864820e-03 1.203657e-02 9.279489e-03
## R-HSA-3000480      2/38  19/10654 2.038787e-03 1.258729e-02 9.704065e-03
## R-HSA-76002        5/38 262/10654 2.237056e-03 1.323592e-02 1.020412e-02
## R-HSA-140877       2/38  39/10654 8.447210e-03 4.798015e-02 3.698989e-02
##                                                                   geneID Count
## R-HSA-1236977                                         567/3105/3106/3133     4
## R-HSA-6798695 567/929/1471/1508/1075/1509/2512/2896/3106/10577/5660/7305    12
## R-HSA-1236975                                567/929/3105/3106/3133/4360     6
## R-HSA-983170                                          567/3105/3106/3133     4
## R-HSA-2132295                               972/1508/1075/1509/3122/5641     6
## R-HSA-198933                                567/2213/3105/3106/3133/7305     6
## R-HSA-1236974                                     567/929/3105/3106/3133     5
## R-HSA-2173782                                       9332/2512/8685/23166     4
## R-HSA-166786                                                 712/713/714     3
## R-HSA-877300                                     567/3105/3106/3122/3133     5
## R-HSA-166663                                                 712/713/714     3
## R-HSA-114608                                       2/2162/5660/6414/7114     5
## R-HSA-76005                                        2/2162/5660/6414/7114     5
## R-HSA-2424491                                              567/3133/7305     3
## R-HSA-2172127                                              567/3133/7305     3
## R-HSA-977606                                                 712/713/714     3
## R-HSA-913531                                     567/3105/3106/3122/3133     5
## R-HSA-1679131                                                  1508/5641     2
## R-HSA-166658                                                 712/713/714     3
## R-HSA-983169                                 567/929/3105/3106/3133/4360     6
## R-HSA-174824                                                2/10577/5360     3
## R-HSA-909733                                              3105/3106/3133     3
## R-HSA-3000480                                                  2512/8685     2
## R-HSA-76002                                        2/2162/5660/6414/7114     5
## R-HSA-140877                                                      2/2162     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_9"
##  [1] "ABI3BP"  "ACKR3"   "ACTG1"   "ADD3"    "AHNAK"   "C1R"     "C1S"    
##  [8] "C3"      "CCDC80"  "CD55"    "CFD"     "CILP"    "CLEC3B"  "COL1A1" 
## [15] "COL1A2"  "COL3A1"  "COL6A1"  "COL6A2"  "COL6A3"  "CPE"     "DCN"    
## [22] "EFEMP1"  "EMP3"    "FBLN1"   "FBLN2"   "FBN1"    "FN1"     "FNDC1"  
## [29] "FSTL1"   "GPNMB"   "GSN"     "HTRA3"   "IGFBP5"  "IGFBP6"  "LUM"    
## [36] "MARCKS"  "MFAP5"   "MMP2"    "MYADM"   "PI16"    "PMP22"   "PRG4"   
## [43] "PTGIS"   "S100A10" "S100A4"  "S100A6"  "SCARA5"  "SEMA3C"  "SFRP4"  
## [50] "TIMP2"   "TNXB"    "VCAN"   
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0005201 GO:0005201
## GO:0005539 GO:0005539
## GO:0030020 GO:0030020
## GO:0048407 GO:0048407
## GO:0008201 GO:0008201
## GO:0019838 GO:0019838
## GO:0030021 GO:0030021
## GO:1901681 GO:1901681
## GO:0001968 GO:0001968
## GO:0005178 GO:0005178
## GO:0097493 GO:0097493
## GO:0002020 GO:0002020
## GO:0061134 GO:0061134
## GO:0005518 GO:0005518
## GO:0005520 GO:0005520
## GO:0050839 GO:0050839
## GO:0004252 GO:0004252
## GO:0008236 GO:0008236
## GO:0017171 GO:0017171
## GO:0005044 GO:0005044
## GO:0031994 GO:0031994
## GO:0044548 GO:0044548
## GO:0030414 GO:0030414
## GO:0038024 GO:0038024
## GO:0043394 GO:0043394
## GO:0016504 GO:0016504
## GO:0004175 GO:0004175
## GO:0050840 GO:0050840
## GO:0048306 GO:0048306
## GO:0004866 GO:0004866
##                                                                              Description
## GO:0005201                                   extracellular matrix structural constituent
## GO:0005539                                                     glycosaminoglycan binding
## GO:0030020       extracellular matrix structural constituent conferring tensile strength
## GO:0048407                                        platelet-derived growth factor binding
## GO:0008201                                                               heparin binding
## GO:0019838                                                         growth factor binding
## GO:0030021 extracellular matrix structural constituent conferring compression resistance
## GO:1901681                                                       sulfur compound binding
## GO:0001968                                                           fibronectin binding
## GO:0005178                                                              integrin binding
## GO:0097493                            structural molecule activity conferring elasticity
## GO:0002020                                                              protease binding
## GO:0061134                                                  peptidase regulator activity
## GO:0005518                                                              collagen binding
## GO:0005520                                            insulin-like growth factor binding
## GO:0050839                                                cell adhesion molecule binding
## GO:0004252                                            serine-type endopeptidase activity
## GO:0008236                                                serine-type peptidase activity
## GO:0017171                                                     serine hydrolase activity
## GO:0005044                                                   scavenger receptor activity
## GO:0031994                                          insulin-like growth factor I binding
## GO:0044548                                                          S100 protein binding
## GO:0030414                                                  peptidase inhibitor activity
## GO:0038024                                                       cargo receptor activity
## GO:0043394                                                          proteoglycan binding
## GO:0016504                                                  peptidase activator activity
## GO:0004175                                                        endopeptidase activity
## GO:0050840                                                  extracellular matrix binding
## GO:0048306                                             calcium-dependent protein binding
## GO:0004866                                              endopeptidase inhibitor activity
##            GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## GO:0005201     19/51 163/17697 2.686161e-26 2.793607e-24 1.639972e-24
## GO:0005539     10/51 229/17697 8.689308e-10 4.518440e-08 2.652525e-08
## GO:0030020      6/51  41/17697 1.759900e-09 6.100986e-08 3.581551e-08
## GO:0048407      4/51  11/17697 1.988719e-08 5.170670e-07 3.035414e-07
## GO:0008201      8/51 169/17697 2.630203e-08 5.470822e-07 3.211616e-07
## GO:0019838      7/51 137/17697 1.244806e-07 2.157665e-06 1.266645e-06
## GO:0030021      4/51  22/17697 4.306415e-07 6.398103e-06 3.755971e-06
## GO:1901681      8/51 250/17697 5.344217e-07 6.947482e-06 4.078481e-06
## GO:0001968      4/51  27/17697 1.022264e-06 1.181283e-05 6.934656e-06
## GO:0005178      6/51 132/17697 2.100892e-06 2.184928e-05 1.282650e-05
## GO:0097493      3/51  11/17697 3.660337e-06 3.460682e-05 2.031574e-05
## GO:0002020      5/51 128/17697 3.293044e-05 2.853971e-04 1.675408e-04
## GO:0061134      6/51 219/17697 3.794776e-05 3.035821e-04 1.782162e-04
## GO:0005518      4/51  67/17697 4.101074e-05 3.046512e-04 1.788438e-04
## GO:0005520      3/51  28/17697 7.020473e-05 4.867528e-04 2.857455e-04
## GO:0050839      8/51 499/17697 8.280610e-05 5.382396e-04 3.159706e-04
## GO:0004252      5/51 160/17697 9.528047e-05 5.828923e-04 3.421837e-04
## GO:0008236      5/51 182/17697 1.743551e-04 1.007385e-03 5.913798e-04
## GO:0017171      5/51 186/17697 1.929335e-04 1.056057e-03 6.199524e-04
## GO:0005044      3/51  51/17697 4.259233e-04 2.214801e-03 1.300187e-03
## GO:0031994      2/51  12/17697 5.275836e-04 2.612795e-03 1.533827e-03
## GO:0044548      2/51  15/17697 8.347073e-04 3.945889e-03 2.316413e-03
## GO:0030414      4/51 182/17697 1.855199e-03 8.171503e-03 4.797036e-03
## GO:0038024      3/51  85/17697 1.885732e-03 8.171503e-03 4.797036e-03
## GO:0043394      2/51  36/17697 4.818446e-03 2.004474e-02 1.176715e-02
## GO:0016504      2/51  38/17697 5.357071e-03 2.142828e-02 1.257936e-02
## GO:0004175      5/51 427/17697 7.545067e-03 2.906248e-02 1.706097e-02
## GO:0050840      2/51  57/17697 1.174598e-02 4.362793e-02 2.561154e-02
## GO:0048306      2/51  61/17697 1.337003e-02 4.794770e-02 2.814744e-02
## GO:0004866      3/51 175/17697 1.398635e-02 4.848603e-02 2.846346e-02
##                                                                                                      geneID
## GO:0005201 25890/8483/1277/1278/1281/1291/1292/1293/1634/2202/2192/2199/2200/2335/4060/8076/10216/7148/1462
## GO:0005539                                           25890/151887/7123/1634/2200/2335/11167/10457/7148/1462
## GO:0030020                                                                    1277/1278/1281/1291/1292/1293
## GO:0048407                                                                              1277/1278/1281/1291
## GO:0008201                                                     25890/151887/7123/2200/2335/11167/10457/7148
## GO:0019838                                                              1277/1278/1281/1291/94031/3488/3489
## GO:0030021                                                                             1634/4060/10216/1462
## GO:1901681                                                     25890/151887/7123/2200/2335/11167/10457/7148
## GO:0001968                                                                            151887/2192/3488/3489
## GO:0005178                                                                   1281/2200/2335/10457/7077/7148
## GO:0097493                                                                                  79026/2199/2200
## GO:0002020                                                                         1277/1278/1281/2335/7077
## GO:0061134                                                                   718/1293/2192/2335/221476/7077
## GO:0005518                                                                             25890/1634/2335/4060
## GO:0005520                                                                                  94031/3488/3489
## GO:0050839                                                        79026/1281/1363/2200/2335/10457/7077/7148
## GO:0004252                                                                          715/716/1675/94031/4313
## GO:0008236                                                                          715/716/1675/94031/4313
## GO:0017171                                                                          715/716/1675/94031/4313
## GO:0005044                                                                               57007/10216/286133
## GO:0031994                                                                                        3488/3489
## GO:0044548                                                                                       79026/6277
## GO:0030414                                                                             718/1293/221476/7077
## GO:0038024                                                                               57007/10216/286133
## GO:0043394                                                                                       2335/10457
## GO:0016504                                                                                        2192/2335
## GO:0004175                                                                          715/716/1675/94031/4313
## GO:0050840                                                                                        1634/2199
## GO:0048306                                                                                        6275/6277
## GO:0004866                                                                                    718/1293/7077
##            Count
## GO:0005201    19
## GO:0005539    10
## GO:0030020     6
## GO:0048407     4
## GO:0008201     8
## GO:0019838     7
## GO:0030021     4
## GO:1901681     8
## GO:0001968     4
## GO:0005178     6
## GO:0097493     3
## GO:0002020     5
## GO:0061134     6
## GO:0005518     4
## GO:0005520     3
## GO:0050839     8
## GO:0004252     5
## GO:0008236     5
## GO:0017171     5
## GO:0005044     3
## GO:0031994     2
## GO:0044548     2
## GO:0030414     4
## GO:0038024     3
## GO:0043394     2
## GO:0016504     2
## GO:0004175     5
## GO:0050840     2
## GO:0048306     2
## GO:0004866     3
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1474244 R-HSA-1474244
## R-HSA-3000178 R-HSA-3000178
## R-HSA-1474228 R-HSA-1474228
## R-HSA-216083   R-HSA-216083
## R-HSA-1442490 R-HSA-1442490
## R-HSA-2129379 R-HSA-2129379
## R-HSA-8948216 R-HSA-8948216
## R-HSA-1566948 R-HSA-1566948
## R-HSA-381426   R-HSA-381426
## R-HSA-2022090 R-HSA-2022090
## R-HSA-1650814 R-HSA-1650814
## R-HSA-3000480 R-HSA-3000480
## R-HSA-1474290 R-HSA-1474290
## R-HSA-166663   R-HSA-166663
## R-HSA-166658   R-HSA-166658
## R-HSA-8957275 R-HSA-8957275
## R-HSA-3000170 R-HSA-3000170
## R-HSA-8874081 R-HSA-8874081
## R-HSA-8875878 R-HSA-8875878
## R-HSA-2173782 R-HSA-2173782
## R-HSA-419037   R-HSA-419037
## R-HSA-977606   R-HSA-977606
## R-HSA-9006934 R-HSA-9006934
## R-HSA-186797   R-HSA-186797
## R-HSA-3000171 R-HSA-3000171
## R-HSA-375165   R-HSA-375165
## R-HSA-6806834 R-HSA-6806834
## R-HSA-76009     R-HSA-76009
## R-HSA-3560782 R-HSA-3560782
## R-HSA-2022923 R-HSA-2022923
## R-HSA-430116   R-HSA-430116
## R-HSA-166786   R-HSA-166786
## R-HSA-2024101 R-HSA-2024101
## R-HSA-198933   R-HSA-198933
## R-HSA-2214320 R-HSA-2214320
## R-HSA-75892     R-HSA-75892
## R-HSA-2243919 R-HSA-2243919
## R-HSA-76002     R-HSA-76002
## R-HSA-2022870 R-HSA-2022870
## R-HSA-3560783 R-HSA-3560783
## R-HSA-3560801 R-HSA-3560801
## R-HSA-4420332 R-HSA-4420332
## R-HSA-1971475 R-HSA-1971475
## R-HSA-1592389 R-HSA-1592389
## R-HSA-6785807 R-HSA-6785807
## R-HSA-114604   R-HSA-114604
## R-HSA-6802948 R-HSA-6802948
## R-HSA-5674135 R-HSA-5674135
## R-HSA-1630316 R-HSA-1630316
## R-HSA-114608   R-HSA-114608
## R-HSA-76005     R-HSA-76005
## R-HSA-6802946 R-HSA-6802946
## R-HSA-6802949 R-HSA-6802949
## R-HSA-6802955 R-HSA-6802955
## R-HSA-9649948 R-HSA-9649948
## R-HSA-202733   R-HSA-202733
## R-HSA-1793185 R-HSA-1793185
## R-HSA-3928665 R-HSA-3928665
## R-HSA-3781865 R-HSA-3781865
## R-HSA-1638091 R-HSA-1638091
##                                                                                                                               Description
## R-HSA-1474244                                                                                           Extracellular matrix organization
## R-HSA-3000178                                                                                                           ECM proteoglycans
## R-HSA-1474228                                                                                     Degradation of the extracellular matrix
## R-HSA-216083                                                                                           Integrin cell surface interactions
## R-HSA-1442490                                                                                                        Collagen degradation
## R-HSA-2129379                                                                                    Molecules associated with elastic fibres
## R-HSA-8948216                                                                                                Collagen chain trimerization
## R-HSA-1566948                                                                                                     Elastic fibre formation
## R-HSA-381426  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
## R-HSA-2022090                                                                Assembly of collagen fibrils and other multimeric structures
## R-HSA-1650814                                                                                 Collagen biosynthesis and modifying enzymes
## R-HSA-3000480                                                                                             Scavenging by Class A Receptors
## R-HSA-1474290                                                                                                          Collagen formation
## R-HSA-166663                                                                                             Initial triggering of complement
## R-HSA-166658                                                                                                           Complement cascade
## R-HSA-8957275                                                                                  Post-translational protein phosphorylation
## R-HSA-3000170                                                                                                       Syndecan interactions
## R-HSA-8874081                                                                                                MET activates PTK2 signaling
## R-HSA-8875878                                                                                                  MET promotes cell motility
## R-HSA-2173782                                                                        Binding and Uptake of Ligands by Scavenger Receptors
## R-HSA-419037                                                                                                           NCAM1 interactions
## R-HSA-977606                                                                                             Regulation of Complement cascade
## R-HSA-9006934                                                                                      Signaling by Receptor Tyrosine Kinases
## R-HSA-186797                                                                                                            Signaling by PDGF
## R-HSA-3000171                                                                                      Non-integrin membrane-ECM interactions
## R-HSA-375165                                                                                        NCAM signaling for neurite out-growth
## R-HSA-6806834                                                                                                            Signaling by MET
## R-HSA-76009                                                                                         Platelet Aggregation (Plug Formation)
## R-HSA-3560782                                                                       Diseases associated with glycosaminoglycan metabolism
## R-HSA-2022923                                                                                               Dermatan sulfate biosynthesis
## R-HSA-430116                                                                                              GP1b-IX-V activation signalling
## R-HSA-166786                                                                                             Creation of C4 and C2 activators
## R-HSA-2024101                                                                                                           CS/DS degradation
## R-HSA-198933                                                     Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-2214320                                                                                                  Anchoring fibril formation
## R-HSA-75892                                                                                         Platelet Adhesion to exposed collagen
## R-HSA-2243919                                                                                            Crosslinking of collagen fibrils
## R-HSA-76002                                                                                Platelet activation, signaling and aggregation
## R-HSA-2022870                                                                                            Chondroitin sulfate biosynthesis
## R-HSA-3560783                                                                                Defective B4GALT7 causes EDS, progeroid type
## R-HSA-3560801                                                                                             Defective B3GAT3 causes JDSSDHD
## R-HSA-4420332                                                                                  Defective B3GALT6 causes EDSP2 and SEMDJL1
## R-HSA-1971475                                                             A tetrasaccharide linker sequence is required for GAG synthesis
## R-HSA-1592389                                                                                     Activation of Matrix Metalloproteinases
## R-HSA-6785807                                                                                  Interleukin-4 and Interleukin-13 signaling
## R-HSA-114604                                                                                             GPVI-mediated activation cascade
## R-HSA-6802948                                                                              Signaling by high-kinase activity BRAF mutants
## R-HSA-5674135                                                                                                   MAP2K and MAPK activation
## R-HSA-1630316                                                                                                Glycosaminoglycan metabolism
## R-HSA-114608                                                                                                      Platelet degranulation 
## R-HSA-76005                                                                                  Response to elevated platelet cytosolic Ca2+
## R-HSA-6802946                                                                          Signaling by moderate kinase activity BRAF mutants
## R-HSA-6802949                                                                                                    Signaling by RAS mutants
## R-HSA-6802955                                                             Paradoxical activation of RAF signaling by kinase inactive BRAF
## R-HSA-9649948                                                                                         Signaling downstream of RAS mutants
## R-HSA-202733                                                                               Cell surface interactions at the vascular wall
## R-HSA-1793185                                                                             Chondroitin sulfate/dermatan sulfate metabolism
## R-HSA-3928665                                                                                      EPH-ephrin mediated repulsion of cells
## R-HSA-3781865                                                                                                   Diseases of glycosylation
## R-HSA-1638091                                                                                 Heparan sulfate/heparin (HS-GAG) metabolism
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1474244     18/38 301/10654 1.600710e-18 2.465093e-16 1.381665e-16
## R-HSA-3000178     11/38  76/10654 1.183612e-15 9.113810e-14 5.108219e-14
## R-HSA-1474228     11/38 140/10654 1.205930e-12 6.190440e-11 3.469693e-11
## R-HSA-216083       9/38  85/10654 1.146146e-11 4.412661e-10 2.473262e-10
## R-HSA-1442490      7/38  64/10654 2.196778e-09 6.766076e-08 3.792333e-08
## R-HSA-2129379      6/38  38/10654 3.459710e-09 8.879923e-08 4.977127e-08
## R-HSA-8948216      6/38  44/10654 8.710488e-09 1.785762e-07 1.000905e-07
## R-HSA-1566948      6/38  45/10654 1.002465e-08 1.785762e-07 1.000905e-07
## R-HSA-381426       8/38 125/10654 1.043627e-08 1.785762e-07 1.000905e-07
## R-HSA-2022090      6/38  61/10654 6.557235e-08 1.009814e-06 5.659929e-07
## R-HSA-1650814      6/38  67/10654 1.160405e-07 1.624567e-06 9.105570e-07
## R-HSA-3000480      4/38  19/10654 5.131895e-07 6.585932e-06 3.691363e-06
## R-HSA-1474290      6/38  90/10654 6.821867e-07 8.081288e-06 4.529498e-06
## R-HSA-166663       4/38  23/10654 1.160492e-06 1.276542e-05 7.154916e-06
## R-HSA-166658       5/38  58/10654 1.754765e-06 1.801559e-05 1.009759e-05
## R-HSA-8957275      6/38 108/10654 2.001299e-06 1.926251e-05 1.079648e-05
## R-HSA-3000170      4/38  27/10654 2.276623e-06 2.062353e-05 1.155932e-05
## R-HSA-8874081      4/38  30/10654 3.527885e-06 3.018301e-05 1.691734e-05
## R-HSA-8875878      4/38  41/10654 1.267535e-05 1.024750e-04 5.743642e-05
## R-HSA-2173782      4/38  42/10654 1.397386e-05 1.024750e-04 5.743642e-05
## R-HSA-419037       4/38  42/10654 1.397386e-05 1.024750e-04 5.743642e-05
## R-HSA-977606       4/38  47/10654 2.198534e-05 1.538974e-04 8.625828e-05
## R-HSA-9006934      9/38 473/10654 3.199443e-05 2.142236e-04 1.200706e-04
## R-HSA-186797       4/38  58/10654 5.084723e-05 3.262697e-04 1.828716e-04
## R-HSA-3000171      4/38  59/10654 5.440613e-05 3.351418e-04 1.878443e-04
## R-HSA-375165       4/38  63/10654 7.048288e-05 4.174755e-04 2.339918e-04
## R-HSA-6806834      4/38  79/10654 1.706727e-04 9.734662e-04 5.456202e-04
## R-HSA-76009        3/38  39/10654 3.501487e-04 1.925818e-03 1.079406e-03
## R-HSA-3560782      3/38  41/10654 4.064198e-04 2.158229e-03 1.209671e-03
## R-HSA-2022923      2/38  11/10654 6.676585e-04 3.427314e-03 1.920982e-03
## R-HSA-430116       2/38  12/10654 7.993885e-04 3.971156e-03 2.225802e-03
## R-HSA-166786       2/38  14/10654 1.097237e-03 5.120440e-03 2.869966e-03
## R-HSA-2024101      2/38  14/10654 1.097237e-03 5.120440e-03 2.869966e-03
## R-HSA-198933       4/38 132/10654 1.199090e-03 5.403679e-03 3.028720e-03
## R-HSA-2214320      2/38  15/10654 1.263198e-03 5.403679e-03 3.028720e-03
## R-HSA-75892        2/38  15/10654 1.263198e-03 5.403679e-03 3.028720e-03
## R-HSA-2243919      2/38  18/10654 1.828283e-03 7.609610e-03 4.265127e-03
## R-HSA-76002        5/38 262/10654 2.237056e-03 8.287522e-03 4.645091e-03
## R-HSA-2022870      2/38  20/10654 2.260233e-03 8.287522e-03 4.645091e-03
## R-HSA-3560783      2/38  20/10654 2.260233e-03 8.287522e-03 4.645091e-03
## R-HSA-3560801      2/38  20/10654 2.260233e-03 8.287522e-03 4.645091e-03
## R-HSA-4420332      2/38  20/10654 2.260233e-03 8.287522e-03 4.645091e-03
## R-HSA-1971475      2/38  26/10654 3.814443e-03 1.366103e-02 7.656900e-03
## R-HSA-1592389      2/38  33/10654 6.100483e-03 2.135169e-02 1.196746e-02
## R-HSA-6785807      3/38 108/10654 6.604855e-03 2.260328e-02 1.266896e-02
## R-HSA-114604       2/38  35/10654 6.843864e-03 2.291207e-02 1.284203e-02
## R-HSA-6802948      2/38  36/10654 7.230233e-03 2.369055e-02 1.327837e-02
## R-HSA-5674135      2/38  40/10654 8.871926e-03 2.846410e-02 1.595390e-02
## R-HSA-1630316      3/38 124/10654 9.648915e-03 3.032516e-02 1.699702e-02
## R-HSA-114608       3/38 129/10654 1.074241e-02 3.308664e-02 1.854480e-02
## R-HSA-76005        3/38 134/10654 1.190525e-02 3.389305e-02 1.899679e-02
## R-HSA-6802946      2/38  47/10654 1.210466e-02 3.389305e-02 1.899679e-02
## R-HSA-6802949      2/38  47/10654 1.210466e-02 3.389305e-02 1.899679e-02
## R-HSA-6802955      2/38  47/10654 1.210466e-02 3.389305e-02 1.899679e-02
## R-HSA-9649948      2/38  47/10654 1.210466e-02 3.389305e-02 1.899679e-02
## R-HSA-202733       3/38 137/10654 1.263654e-02 3.475050e-02 1.947738e-02
## R-HSA-1793185      2/38  50/10654 1.362553e-02 3.681284e-02 2.063331e-02
## R-HSA-3928665      2/38  51/10654 1.415006e-02 3.700025e-02 2.073835e-02
## R-HSA-3781865      3/38 143/10654 1.417542e-02 3.700025e-02 2.073835e-02
## R-HSA-1638091      2/38  55/10654 1.633424e-02 4.192456e-02 2.349838e-02
##                                                                                                  geneID
## R-HSA-1474244 1277/1278/1281/1291/1292/1293/1634/2202/2192/2199/2200/2335/4060/8076/4313/7077/7148/1462
## R-HSA-3000178                                    1277/1278/1281/1291/1292/1293/1634/2335/4060/7148/1462
## R-HSA-1474228                                    1277/1278/1281/1291/1292/1293/1634/2200/2335/4313/7077
## R-HSA-216083                                               1277/1278/1281/1291/1292/1293/2200/2335/4060
## R-HSA-1442490                                                        1277/1278/1281/1291/1292/1293/4313
## R-HSA-2129379                                                             2202/2192/2199/2200/2335/8076
## R-HSA-8948216                                                             1277/1278/1281/1291/1292/1293
## R-HSA-1566948                                                             2202/2192/2199/2200/2335/8076
## R-HSA-381426                                                    718/2200/2335/11167/3488/3489/4313/1462
## R-HSA-2022090                                                             1277/1278/1281/1291/1292/1293
## R-HSA-1650814                                                             1277/1278/1281/1291/1292/1293
## R-HSA-3000480                                                                     1277/1278/1281/286133
## R-HSA-1474290                                                             1277/1278/1281/1291/1292/1293
## R-HSA-166663                                                                           715/716/718/1675
## R-HSA-166658                                                                      715/716/718/1604/1675
## R-HSA-8957275                                                             718/2200/2335/11167/3488/1462
## R-HSA-3000170                                                                       1277/1278/1281/2335
## R-HSA-8874081                                                                       1277/1278/1281/2335
## R-HSA-8875878                                                                       1277/1278/1281/2335
## R-HSA-2173782                                                                     1277/1278/1281/286133
## R-HSA-419037                                                                        1281/1291/1292/1293
## R-HSA-977606                                                                           715/716/718/1604
## R-HSA-9006934                                                71/8483/1277/1278/1281/1291/1292/1293/2335
## R-HSA-186797                                                                        1281/1291/1292/1293
## R-HSA-3000171                                                                       1277/1278/1281/2335
## R-HSA-375165                                                                        1281/1291/1292/1293
## R-HSA-6806834                                                                       1277/1278/1281/2335
## R-HSA-76009                                                                              1277/1278/2335
## R-HSA-3560782                                                                            1634/4060/1462
## R-HSA-2022923                                                                                 1634/1462
## R-HSA-430116                                                                                  1277/1278
## R-HSA-166786                                                                                    715/716
## R-HSA-2024101                                                                                 1634/1462
## R-HSA-198933                                                                         718/1277/1278/1281
## R-HSA-2214320                                                                                 1277/1278
## R-HSA-75892                                                                                   1277/1278
## R-HSA-2243919                                                                                 1277/1278
## R-HSA-76002                                                                    1675/7123/1277/1278/2335
## R-HSA-2022870                                                                                 1634/1462
## R-HSA-3560783                                                                                 1634/1462
## R-HSA-3560801                                                                                 1634/1462
## R-HSA-4420332                                                                                 1634/1462
## R-HSA-1971475                                                                                 1634/1462
## R-HSA-1592389                                                                                 4313/7077
## R-HSA-6785807                                                                            1278/2335/4313
## R-HSA-114604                                                                                  1277/1278
## R-HSA-6802948                                                                                   71/2335
## R-HSA-5674135                                                                                   71/2335
## R-HSA-1630316                                                                            1634/4060/1462
## R-HSA-114608                                                                             1675/7123/2335
## R-HSA-76005                                                                              1675/7123/2335
## R-HSA-6802946                                                                                   71/2335
## R-HSA-6802949                                                                                   71/2335
## R-HSA-6802955                                                                                   71/2335
## R-HSA-9649948                                                                                   71/2335
## R-HSA-202733                                                                             1277/1278/2335
## R-HSA-1793185                                                                                 1634/1462
## R-HSA-3928665                                                                                   71/4313
## R-HSA-3781865                                                                            1634/4060/1462
## R-HSA-1638091                                                                                 1634/1462
##               Count
## R-HSA-1474244    18
## R-HSA-3000178    11
## R-HSA-1474228    11
## R-HSA-216083      9
## R-HSA-1442490     7
## R-HSA-2129379     6
## R-HSA-8948216     6
## R-HSA-1566948     6
## R-HSA-381426      8
## R-HSA-2022090     6
## R-HSA-1650814     6
## R-HSA-3000480     4
## R-HSA-1474290     6
## R-HSA-166663      4
## R-HSA-166658      5
## R-HSA-8957275     6
## R-HSA-3000170     4
## R-HSA-8874081     4
## R-HSA-8875878     4
## R-HSA-2173782     4
## R-HSA-419037      4
## R-HSA-977606      4
## R-HSA-9006934     9
## R-HSA-186797      4
## R-HSA-3000171     4
## R-HSA-375165      4
## R-HSA-6806834     4
## R-HSA-76009       3
## R-HSA-3560782     3
## R-HSA-2022923     2
## R-HSA-430116      2
## R-HSA-166786      2
## R-HSA-2024101     2
## R-HSA-198933      4
## R-HSA-2214320     2
## R-HSA-75892       2
## R-HSA-2243919     2
## R-HSA-76002       5
## R-HSA-2022870     2
## R-HSA-3560783     2
## R-HSA-3560801     2
## R-HSA-4420332     2
## R-HSA-1971475     2
## R-HSA-1592389     2
## R-HSA-6785807     3
## R-HSA-114604      2
## R-HSA-6802948     2
## R-HSA-5674135     2
## R-HSA-1630316     3
## R-HSA-114608      3
## R-HSA-76005       3
## R-HSA-6802946     2
## R-HSA-6802949     2
## R-HSA-6802955     2
## R-HSA-9649948     2
## R-HSA-202733      3
## R-HSA-1793185     2
## R-HSA-3928665     2
## R-HSA-3781865     3
## R-HSA-1638091     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_10"
##  [1] "APOD"   "CMA1"   "COL1A2" "CPA3"   "CTSG"   "CXCL14" "DCN"    "HPGD"  
##  [9] "KIT"    "MGP"    "MS4A2"  "TPSAB1" "TPSB2" 
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                                 Description GeneRatio
## GO:0004252 GO:0004252          serine-type endopeptidase activity      4/13
## GO:0008236 GO:0008236              serine-type peptidase activity      4/13
## GO:0017171 GO:0017171                   serine hydrolase activity      4/13
## GO:0004175 GO:0004175                      endopeptidase activity      4/13
## GO:0005201 GO:0005201 extracellular matrix structural constituent      3/13
## GO:0002020 GO:0002020                            protease binding      2/13
## GO:0004955 GO:0004955             prostaglandin receptor activity      1/13
## GO:0004954 GO:0004954                prostanoid receptor activity      1/13
## GO:0048407 GO:0048407      platelet-derived growth factor binding      1/13
##              BgRatio       pvalue     p.adjust       qvalue
## GO:0004252 160/17697 4.318058e-06 0.0001333515 6.605646e-05
## GO:0008236 182/17697 7.197501e-06 0.0001333515 6.605646e-05
## GO:0017171 186/17697 7.844205e-06 0.0001333515 6.605646e-05
## GO:0004175 427/17697 2.010023e-04 0.0020910787 1.035828e-03
## GO:0005201 163/17697 2.050077e-04 0.0020910787 1.035828e-03
## GO:0002020 128/17697 3.842951e-03 0.0326650819 1.618085e-02
## GO:0004955  10/17697 7.323499e-03 0.0456343413 2.260525e-02
## GO:0004954  11/17697 8.053119e-03 0.0456343413 2.260525e-02
## GO:0048407  11/17697 8.053119e-03 0.0456343413 2.260525e-02
##                          geneID Count
## GO:0004252 1215/1511/7177/64499     4
## GO:0008236 1215/1511/7177/64499     4
## GO:0017171 1215/1511/7177/64499     4
## GO:0004175 1215/1511/7177/64499     4
## GO:0005201       1278/1634/4256     3
## GO:0002020            1278/3815     2
## GO:0004955                 3248     1
## GO:0004954                 3248     1
## GO:0048407                 1278     1
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID                                   Description
## R-HSA-1474228 R-HSA-1474228       Degradation of the extracellular matrix
## R-HSA-2022377 R-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
## R-HSA-1592389 R-HSA-1592389       Activation of Matrix Metalloproteinases
## R-HSA-1474244 R-HSA-1474244             Extracellular matrix organization
## R-HSA-2980736 R-HSA-2980736                    Peptide hormone metabolism
## R-HSA-1433557 R-HSA-1433557                          Signaling by SCF-KIT
## R-HSA-3000178 R-HSA-3000178                             ECM proteoglycans
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1474228      5/10 140/10654 8.719154e-08 6.800940e-06 3.395881e-06
## R-HSA-2022377      3/10  18/10654 4.823853e-07 1.881303e-05 9.393820e-06
## R-HSA-1592389      3/10  33/10654 3.201574e-06 7.616976e-05 3.803349e-05
## R-HSA-1474244      5/10 301/10654 3.906142e-06 7.616976e-05 3.803349e-05
## R-HSA-2980736      3/10  90/10654 6.702215e-05 1.045546e-03 5.220673e-04
## R-HSA-1433557      2/10  43/10654 7.014985e-04 9.119481e-03 4.553587e-03
## R-HSA-3000178      2/10  76/10654 2.177727e-03 2.426610e-02 1.211667e-02
##                                 geneID Count
## R-HSA-1474228 1215/1278/1511/1634/7177     5
## R-HSA-2022377           1215/1359/1511     3
## R-HSA-1592389           1215/1511/7177     3
## R-HSA-1474244 1215/1278/1511/1634/7177     5
## R-HSA-2980736           1215/1359/1511     3
## R-HSA-1433557                1215/3815     2
## R-HSA-3000178                1278/1634     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_11"
## [1] "ACTB"   "DDX21"  "IFITM3" "MT1X"   "MT2A"   "NNMT"   "PTMA"   "SAA2"  
## [9] "SOD2"  
## [1] "---------------------------------"
## [1] "GO Enrichment: "
## [1] ID          Description GeneRatio   BgRatio     pvalue      p.adjust   
## [7] qvalue      geneID      Count      
## <0 rows> (or 0-length row.names)
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID                                         Description
## R-HSA-5661231 R-HSA-5661231                        Metallothioneins bind metals
## R-HSA-5660526 R-HSA-5660526                              Response to metal ions
## R-HSA-5250924 R-HSA-5250924 B-WICH complex positively regulates rRNA expression
## R-HSA-5250913 R-HSA-5250913   Positive epigenetic regulation of rRNA expression
##               GeneRatio   BgRatio       pvalue    p.adjust       qvalue
## R-HSA-5661231       2/7  11/10654 2.029569e-05 0.001492914 0.0007416011
## R-HSA-5660526       2/7  14/10654 3.354862e-05 0.001492914 0.0007416011
## R-HSA-5250924       2/7  91/10654 1.473685e-03 0.043719322 0.0217174634
## R-HSA-5250913       2/7 106/10654 1.993292e-03 0.044350753 0.0220311248
##                  geneID Count
## R-HSA-5661231 4501/4502     2
## R-HSA-5660526 4501/4502     2
## R-HSA-5250924   60/9188     2
## R-HSA-5250913   60/9188     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## Warning in clusterProfiler::bitr(d$gene_name, fromType = "SYMBOL", toType =
## "ENTREZID", : 2.7% of input gene IDs are fail to map...
## [1] "cluster_12"
##  [1] "AEBP1"  "APOD"   "C1R"    "C1S"    "C3"     "CCDC80" "CFD"    "CFH"   
##  [9] "CILP"   "COL1A1" "COL1A2" "COL3A1" "COL6A1" "COL6A2" "COL6A3" "CXCL12"
## [17] "DCN"    "FBLN1"  "FBLN2"  "FBN1"   "FN1"    "FSTL1"  "GPC3"   "GPX3"  
## [25] "GSN"    "IGFBP6" "LUM"    "MARCKS" "MFAP4"  "MFAP5"  "MGP"    "MMP2"  
## [33] "PLPP3"  "TIMP2"  "TNXB"   "VCAN"   "WISP2" 
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0005201 GO:0005201
## GO:0030020 GO:0030020
## GO:0048407 GO:0048407
## GO:0005539 GO:0005539
## GO:0005178 GO:0005178
## GO:0008201 GO:0008201
## GO:0061134 GO:0061134
## GO:0002020 GO:0002020
## GO:0019838 GO:0019838
## GO:0005518 GO:0005518
## GO:1901681 GO:1901681
## GO:0030021 GO:0030021
## GO:0001968 GO:0001968
## GO:0097493 GO:0097493
## GO:0004252 GO:0004252
## GO:0050839 GO:0050839
## GO:0008236 GO:0008236
## GO:0030414 GO:0030414
## GO:0017171 GO:0017171
## GO:0043394 GO:0043394
## GO:0016504 GO:0016504
## GO:0004866 GO:0004866
## GO:0061135 GO:0061135
## GO:0050840 GO:0050840
## GO:0004857 GO:0004857
## GO:0004175 GO:0004175
## GO:0046332 GO:0046332
##                                                                              Description
## GO:0005201                                   extracellular matrix structural constituent
## GO:0030020       extracellular matrix structural constituent conferring tensile strength
## GO:0048407                                        platelet-derived growth factor binding
## GO:0005539                                                     glycosaminoglycan binding
## GO:0005178                                                              integrin binding
## GO:0008201                                                               heparin binding
## GO:0061134                                                  peptidase regulator activity
## GO:0002020                                                              protease binding
## GO:0019838                                                         growth factor binding
## GO:0005518                                                              collagen binding
## GO:1901681                                                       sulfur compound binding
## GO:0030021 extracellular matrix structural constituent conferring compression resistance
## GO:0001968                                                           fibronectin binding
## GO:0097493                            structural molecule activity conferring elasticity
## GO:0004252                                            serine-type endopeptidase activity
## GO:0050839                                                cell adhesion molecule binding
## GO:0008236                                                serine-type peptidase activity
## GO:0030414                                                  peptidase inhibitor activity
## GO:0017171                                                     serine hydrolase activity
## GO:0043394                                                          proteoglycan binding
## GO:0016504                                                  peptidase activator activity
## GO:0004866                                              endopeptidase inhibitor activity
## GO:0061135                                              endopeptidase regulator activity
## GO:0050840                                                  extracellular matrix binding
## GO:0004857                                                     enzyme inhibitor activity
## GO:0004175                                                        endopeptidase activity
## GO:0046332                                                                  SMAD binding
##            GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## GO:0005201     19/36 163/17697 5.355184e-30 4.230596e-28 2.423926e-28
## GO:0030020      6/36  41/17697 1.952504e-10 7.712390e-09 4.418824e-09
## GO:0048407      4/36  11/17697 4.710037e-09 1.240310e-07 7.106372e-08
## GO:0005539      8/36 229/17697 1.540728e-08 3.042938e-07 1.743455e-07
## GO:0005178      6/36 132/17697 2.490094e-07 3.934348e-06 2.254190e-06
## GO:0008201      6/36 169/17697 1.065950e-06 1.403501e-05 8.041378e-06
## GO:0061134      6/36 219/17697 4.790294e-06 5.406189e-05 3.097484e-05
## GO:0002020      5/36 128/17697 5.763819e-06 5.691771e-05 3.261108e-05
## GO:0019838      5/36 137/17697 8.032092e-06 7.050391e-05 4.039531e-05
## GO:0005518      4/36  67/17697 1.008819e-05 7.339336e-05 4.205083e-05
## GO:1901681      6/36 250/17697 1.021933e-05 7.339336e-05 4.205083e-05
## GO:0030021      3/36  22/17697 1.159310e-05 7.632125e-05 4.372837e-05
## GO:0001968      3/36  27/17697 2.186595e-05 1.328777e-04 7.613246e-05
## GO:0097493      2/36  11/17697 2.187514e-04 1.234383e-03 7.072413e-04
## GO:0004252      4/36 160/17697 3.025442e-04 1.593400e-03 9.129405e-04
## GO:0050839      6/36 499/17697 4.626610e-04 2.163451e-03 1.239552e-03
## GO:0008236      4/36 182/17697 4.929381e-04 2.163451e-03 1.239552e-03
## GO:0030414      4/36 182/17697 4.929381e-04 2.163451e-03 1.239552e-03
## GO:0017171      4/36 186/17697 5.350106e-04 2.224518e-03 1.274540e-03
## GO:0043394      2/36  36/17697 2.426870e-03 9.586138e-03 5.492391e-03
## GO:0016504      2/36  38/17697 2.701174e-03 1.016156e-02 5.822080e-03
## GO:0004866      3/36 175/17697 5.340734e-03 1.917809e-02 1.098811e-02
## GO:0061135      3/36 182/17697 5.953517e-03 1.970272e-02 1.128870e-02
## GO:0050840      2/36  57/17697 5.985636e-03 1.970272e-02 1.128870e-02
## GO:0004857      4/36 375/17697 6.843708e-03 2.162612e-02 1.239071e-02
## GO:0004175      4/36 427/17697 1.069747e-02 3.250384e-02 1.862312e-02
## GO:0046332      2/36  80/17697 1.150967e-02 3.367643e-02 1.929496e-02
##                                                                                                   geneID
## GO:0005201 165/8483/1277/1278/1281/1291/1292/1293/1634/2192/2199/2200/2335/4060/4239/8076/4256/7148/1462
## GO:0030020                                                                 1277/1278/1281/1291/1292/1293
## GO:0048407                                                                           1277/1278/1281/1291
## GO:0005539                                                    151887/3075/1634/2200/2335/11167/7148/1462
## GO:0005178                                                                 1281/6387/2200/2335/7077/7148
## GO:0008201                                                              151887/3075/2200/2335/11167/7148
## GO:0061134                                                                  718/1293/2192/2335/2719/7077
## GO:0002020                                                                      1277/1278/1281/2335/7077
## GO:0019838                                                                      1277/1278/1281/1291/3489
## GO:0005518                                                                            165/1634/2335/4060
## GO:1901681                                                              151887/3075/2200/2335/11167/7148
## GO:0030021                                                                                1634/4060/1462
## GO:0001968                                                                              151887/2192/3489
## GO:0097493                                                                                     2199/2200
## GO:0004252                                                                             715/716/1675/4313
## GO:0050839                                                                 1281/6387/2200/2335/7077/7148
## GO:0008236                                                                             715/716/1675/4313
## GO:0030414                                                                            718/1293/2719/7077
## GO:0017171                                                                             715/716/1675/4313
## GO:0043394                                                                                     3075/2335
## GO:0016504                                                                                     2192/2335
## GO:0004866                                                                                 718/1293/7077
## GO:0061135                                                                                 718/1293/7077
## GO:0050840                                                                                     1634/2199
## GO:0004857                                                                            718/1293/2719/7077
## GO:0004175                                                                             715/716/1675/4313
## GO:0046332                                                                                     1278/1281
##            Count
## GO:0005201    19
## GO:0030020     6
## GO:0048407     4
## GO:0005539     8
## GO:0005178     6
## GO:0008201     6
## GO:0061134     6
## GO:0002020     5
## GO:0019838     5
## GO:0005518     4
## GO:1901681     6
## GO:0030021     3
## GO:0001968     3
## GO:0097493     2
## GO:0004252     4
## GO:0050839     6
## GO:0008236     4
## GO:0030414     4
## GO:0017171     4
## GO:0043394     2
## GO:0016504     2
## GO:0004866     3
## GO:0061135     3
## GO:0050840     2
## GO:0004857     4
## GO:0004175     4
## GO:0046332     2
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1474244 R-HSA-1474244
## R-HSA-3000178 R-HSA-3000178
## R-HSA-1474228 R-HSA-1474228
## R-HSA-216083   R-HSA-216083
## R-HSA-1442490 R-HSA-1442490
## R-HSA-2129379 R-HSA-2129379
## R-HSA-381426   R-HSA-381426
## R-HSA-8948216 R-HSA-8948216
## R-HSA-1566948 R-HSA-1566948
## R-HSA-2022090 R-HSA-2022090
## R-HSA-1650814 R-HSA-1650814
## R-HSA-1474290 R-HSA-1474290
## R-HSA-166663   R-HSA-166663
## R-HSA-8957275 R-HSA-8957275
## R-HSA-166658   R-HSA-166658
## R-HSA-3000170 R-HSA-3000170
## R-HSA-8874081 R-HSA-8874081
## R-HSA-3560782 R-HSA-3560782
## R-HSA-8875878 R-HSA-8875878
## R-HSA-419037   R-HSA-419037
## R-HSA-9006934 R-HSA-9006934
## R-HSA-977606   R-HSA-977606
## R-HSA-3000480 R-HSA-3000480
## R-HSA-186797   R-HSA-186797
## R-HSA-3560783 R-HSA-3560783
## R-HSA-3560801 R-HSA-3560801
## R-HSA-4420332 R-HSA-4420332
## R-HSA-3000171 R-HSA-3000171
## R-HSA-375165   R-HSA-375165
## R-HSA-1971475 R-HSA-1971475
## R-HSA-6806834 R-HSA-6806834
## R-HSA-76009     R-HSA-76009
## R-HSA-2173782 R-HSA-2173782
## R-HSA-1793185 R-HSA-1793185
## R-HSA-2022923 R-HSA-2022923
## R-HSA-1630316 R-HSA-1630316
## R-HSA-430116   R-HSA-430116
## R-HSA-1638091 R-HSA-1638091
## R-HSA-198933   R-HSA-198933
## R-HSA-166786   R-HSA-166786
## R-HSA-2024101 R-HSA-2024101
## R-HSA-3781865 R-HSA-3781865
## R-HSA-2214320 R-HSA-2214320
## R-HSA-75892     R-HSA-75892
## R-HSA-2243919 R-HSA-2243919
## R-HSA-2022870 R-HSA-2022870
## R-HSA-6785807 R-HSA-6785807
## R-HSA-1592389 R-HSA-1592389
## R-HSA-114604   R-HSA-114604
## R-HSA-76002     R-HSA-76002
## R-HSA-202733   R-HSA-202733
## R-HSA-71387     R-HSA-71387
##                                                                                                                               Description
## R-HSA-1474244                                                                                           Extracellular matrix organization
## R-HSA-3000178                                                                                                           ECM proteoglycans
## R-HSA-1474228                                                                                     Degradation of the extracellular matrix
## R-HSA-216083                                                                                           Integrin cell surface interactions
## R-HSA-1442490                                                                                                        Collagen degradation
## R-HSA-2129379                                                                                    Molecules associated with elastic fibres
## R-HSA-381426  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
## R-HSA-8948216                                                                                                Collagen chain trimerization
## R-HSA-1566948                                                                                                     Elastic fibre formation
## R-HSA-2022090                                                                Assembly of collagen fibrils and other multimeric structures
## R-HSA-1650814                                                                                 Collagen biosynthesis and modifying enzymes
## R-HSA-1474290                                                                                                          Collagen formation
## R-HSA-166663                                                                                             Initial triggering of complement
## R-HSA-8957275                                                                                  Post-translational protein phosphorylation
## R-HSA-166658                                                                                                           Complement cascade
## R-HSA-3000170                                                                                                       Syndecan interactions
## R-HSA-8874081                                                                                                MET activates PTK2 signaling
## R-HSA-3560782                                                                       Diseases associated with glycosaminoglycan metabolism
## R-HSA-8875878                                                                                                  MET promotes cell motility
## R-HSA-419037                                                                                                           NCAM1 interactions
## R-HSA-9006934                                                                                      Signaling by Receptor Tyrosine Kinases
## R-HSA-977606                                                                                             Regulation of Complement cascade
## R-HSA-3000480                                                                                             Scavenging by Class A Receptors
## R-HSA-186797                                                                                                            Signaling by PDGF
## R-HSA-3560783                                                                                Defective B4GALT7 causes EDS, progeroid type
## R-HSA-3560801                                                                                             Defective B3GAT3 causes JDSSDHD
## R-HSA-4420332                                                                                  Defective B3GALT6 causes EDSP2 and SEMDJL1
## R-HSA-3000171                                                                                      Non-integrin membrane-ECM interactions
## R-HSA-375165                                                                                        NCAM signaling for neurite out-growth
## R-HSA-1971475                                                             A tetrasaccharide linker sequence is required for GAG synthesis
## R-HSA-6806834                                                                                                            Signaling by MET
## R-HSA-76009                                                                                         Platelet Aggregation (Plug Formation)
## R-HSA-2173782                                                                        Binding and Uptake of Ligands by Scavenger Receptors
## R-HSA-1793185                                                                             Chondroitin sulfate/dermatan sulfate metabolism
## R-HSA-2022923                                                                                               Dermatan sulfate biosynthesis
## R-HSA-1630316                                                                                                Glycosaminoglycan metabolism
## R-HSA-430116                                                                                              GP1b-IX-V activation signalling
## R-HSA-1638091                                                                                 Heparan sulfate/heparin (HS-GAG) metabolism
## R-HSA-198933                                                     Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-166786                                                                                             Creation of C4 and C2 activators
## R-HSA-2024101                                                                                                           CS/DS degradation
## R-HSA-3781865                                                                                                   Diseases of glycosylation
## R-HSA-2214320                                                                                                  Anchoring fibril formation
## R-HSA-75892                                                                                         Platelet Adhesion to exposed collagen
## R-HSA-2243919                                                                                            Crosslinking of collagen fibrils
## R-HSA-2022870                                                                                            Chondroitin sulfate biosynthesis
## R-HSA-6785807                                                                                  Interleukin-4 and Interleukin-13 signaling
## R-HSA-1592389                                                                                     Activation of Matrix Metalloproteinases
## R-HSA-114604                                                                                             GPVI-mediated activation cascade
## R-HSA-76002                                                                                Platelet activation, signaling and aggregation
## R-HSA-202733                                                                               Cell surface interactions at the vascular wall
## R-HSA-71387                                                                                                   Metabolism of carbohydrates
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1474244     18/33 301/10654 5.617676e-20 6.853565e-18 3.725406e-18
## R-HSA-3000178     11/33  76/10654 1.957921e-16 1.194332e-14 6.492055e-15
## R-HSA-1474228     11/33 140/10654 2.051014e-13 8.340790e-12 4.533820e-12
## R-HSA-216083       9/33  85/10654 2.800548e-12 8.541673e-11 4.643014e-11
## R-HSA-1442490      7/33  64/10654 7.612938e-10 1.857557e-08 1.009716e-08
## R-HSA-2129379      6/33  38/10654 1.406045e-09 2.858958e-08 1.554050e-08
## R-HSA-381426       8/33 125/10654 3.111845e-09 5.411559e-08 2.941572e-08
## R-HSA-8948216      6/33  44/10654 3.548564e-09 5.411559e-08 2.941572e-08
## R-HSA-1566948      6/33  45/10654 4.085585e-09 5.538237e-08 3.010431e-08
## R-HSA-2022090      6/33  61/10654 2.689719e-08 3.281457e-07 1.783708e-07
## R-HSA-1650814      6/33  67/10654 4.771399e-08 5.291916e-07 2.876537e-07
## R-HSA-1474290      6/33  90/10654 2.831153e-07 2.878339e-06 1.564585e-06
## R-HSA-166663       4/33  23/10654 6.479425e-07 6.080691e-06 3.305294e-06
## R-HSA-8957275      6/33 108/10654 8.366037e-07 6.889877e-06 3.745145e-06
## R-HSA-166658       5/33  58/10654 8.471161e-07 6.889877e-06 3.745145e-06
## R-HSA-3000170      4/33  27/10654 1.273027e-06 9.706832e-06 5.276363e-06
## R-HSA-8874081      4/33  30/10654 1.974922e-06 1.417297e-05 7.704031e-06
## R-HSA-3560782      4/33  41/10654 7.125040e-06 4.575026e-05 2.486856e-05
## R-HSA-8875878      4/33  41/10654 7.125040e-06 4.575026e-05 2.486856e-05
## R-HSA-419037       4/33  42/10654 7.857899e-06 4.793318e-05 2.605514e-05
## R-HSA-9006934      9/33 473/10654 9.228657e-06 5.361411e-05 2.914313e-05
## R-HSA-977606       4/33  47/10654 1.238616e-05 6.868689e-05 3.733627e-05
## R-HSA-3000480      3/33  19/10654 2.536568e-05 1.341539e-04 7.292230e-05
## R-HSA-186797       4/33  58/10654 2.876461e-05 1.341539e-04 7.292230e-05
## R-HSA-3560783      3/33  20/10654 2.977900e-05 1.341539e-04 7.292230e-05
## R-HSA-3560801      3/33  20/10654 2.977900e-05 1.341539e-04 7.292230e-05
## R-HSA-4420332      3/33  20/10654 2.977900e-05 1.341539e-04 7.292230e-05
## R-HSA-3000171      4/33  59/10654 3.078942e-05 1.341539e-04 7.292230e-05
## R-HSA-375165       4/33  63/10654 3.994722e-05 1.680538e-04 9.134937e-05
## R-HSA-1971475      3/33  26/10654 6.706182e-05 2.727181e-04 1.482419e-04
## R-HSA-6806834      4/33  79/10654 9.731075e-05 3.829649e-04 2.081690e-04
## R-HSA-76009        3/33  39/10654 2.293426e-04 8.743688e-04 4.752824e-04
## R-HSA-2173782      3/33  42/10654 2.862726e-04 1.058341e-03 5.752846e-04
## R-HSA-1793185      3/33  50/10654 4.805826e-04 1.724443e-03 9.373592e-04
## R-HSA-2022923      2/33  11/10654 5.028708e-04 1.752864e-03 9.528079e-04
## R-HSA-1630316      4/33 124/10654 5.508760e-04 1.866858e-03 1.014772e-03
## R-HSA-430116       2/33  12/10654 6.022760e-04 1.985883e-03 1.079471e-03
## R-HSA-1638091      3/33  55/10654 6.365264e-04 2.043585e-03 1.110836e-03
## R-HSA-198933       4/33 132/10654 6.972672e-04 2.181195e-03 1.185637e-03
## R-HSA-166786       2/33  14/10654 8.271976e-04 2.461417e-03 1.337958e-03
## R-HSA-2024101      2/33  14/10654 8.271976e-04 2.461417e-03 1.337958e-03
## R-HSA-3781865      4/33 143/10654 9.410190e-04 2.641330e-03 1.435753e-03
## R-HSA-2214320      2/33  15/10654 9.526108e-04 2.641330e-03 1.435753e-03
## R-HSA-75892        2/33  15/10654 9.526108e-04 2.641330e-03 1.435753e-03
## R-HSA-2243919      2/33  18/10654 1.380046e-03 3.741458e-03 2.033752e-03
## R-HSA-2022870      2/33  20/10654 1.707158e-03 4.527680e-03 2.461120e-03
## R-HSA-6785807      3/33 108/10654 4.430876e-03 1.150142e-02 6.251852e-03
## R-HSA-1592389      2/33  33/10654 4.626318e-03 1.175856e-02 6.391624e-03
## R-HSA-114604       2/33  35/10654 5.193272e-03 1.293019e-02 7.028488e-03
## R-HSA-76002        4/33 262/10654 8.347974e-03 2.036906e-02 1.107205e-02
## R-HSA-202733       3/33 137/10654 8.561817e-03 2.048121e-02 1.113301e-02
## R-HSA-71387        4/33 295/10654 1.252347e-02 2.938199e-02 1.597123e-02
##                                                                                                  geneID
## R-HSA-1474244 1277/1278/1281/1291/1292/1293/1634/2192/2199/2200/2335/4060/4239/8076/4313/7077/7148/1462
## R-HSA-3000178                                    1277/1278/1281/1291/1292/1293/1634/2335/4060/7148/1462
## R-HSA-1474228                                    1277/1278/1281/1291/1292/1293/1634/2200/2335/4313/7077
## R-HSA-216083                                               1277/1278/1281/1291/1292/1293/2200/2335/4060
## R-HSA-1442490                                                        1277/1278/1281/1291/1292/1293/4313
## R-HSA-2129379                                                             2192/2199/2200/2335/4239/8076
## R-HSA-381426                                                    718/2200/2335/11167/2719/3489/4313/1462
## R-HSA-8948216                                                             1277/1278/1281/1291/1292/1293
## R-HSA-1566948                                                             2192/2199/2200/2335/4239/8076
## R-HSA-2022090                                                             1277/1278/1281/1291/1292/1293
## R-HSA-1650814                                                             1277/1278/1281/1291/1292/1293
## R-HSA-1474290                                                             1277/1278/1281/1291/1292/1293
## R-HSA-166663                                                                           715/716/718/1675
## R-HSA-8957275                                                             718/2200/2335/11167/2719/1462
## R-HSA-166658                                                                      715/716/718/1675/3075
## R-HSA-3000170                                                                       1277/1278/1281/2335
## R-HSA-8874081                                                                       1277/1278/1281/2335
## R-HSA-3560782                                                                       1634/2719/4060/1462
## R-HSA-8875878                                                                       1277/1278/1281/2335
## R-HSA-419037                                                                        1281/1291/1292/1293
## R-HSA-9006934                                              8483/1277/1278/1281/1291/1292/1293/6387/2335
## R-HSA-977606                                                                           715/716/718/3075
## R-HSA-3000480                                                                            1277/1278/1281
## R-HSA-186797                                                                        1281/1291/1292/1293
## R-HSA-3560783                                                                            1634/2719/1462
## R-HSA-3560801                                                                            1634/2719/1462
## R-HSA-4420332                                                                            1634/2719/1462
## R-HSA-3000171                                                                       1277/1278/1281/2335
## R-HSA-375165                                                                        1281/1291/1292/1293
## R-HSA-1971475                                                                            1634/2719/1462
## R-HSA-6806834                                                                       1277/1278/1281/2335
## R-HSA-76009                                                                              1277/1278/2335
## R-HSA-2173782                                                                            1277/1278/1281
## R-HSA-1793185                                                                            1634/2719/1462
## R-HSA-2022923                                                                                 1634/1462
## R-HSA-1630316                                                                       1634/2719/4060/1462
## R-HSA-430116                                                                                  1277/1278
## R-HSA-1638091                                                                            1634/2719/1462
## R-HSA-198933                                                                         718/1277/1278/1281
## R-HSA-166786                                                                                    715/716
## R-HSA-2024101                                                                                 1634/1462
## R-HSA-3781865                                                                       1634/2719/4060/1462
## R-HSA-2214320                                                                                 1277/1278
## R-HSA-75892                                                                                   1277/1278
## R-HSA-2243919                                                                                 1277/1278
## R-HSA-2022870                                                                                 1634/1462
## R-HSA-6785807                                                                            1278/2335/4313
## R-HSA-1592389                                                                                 4313/7077
## R-HSA-114604                                                                                  1277/1278
## R-HSA-76002                                                                         1675/1277/1278/2335
## R-HSA-202733                                                                             1277/1278/2335
## R-HSA-71387                                                                         1634/2719/4060/1462
##               Count
## R-HSA-1474244    18
## R-HSA-3000178    11
## R-HSA-1474228    11
## R-HSA-216083      9
## R-HSA-1442490     7
## R-HSA-2129379     6
## R-HSA-381426      8
## R-HSA-8948216     6
## R-HSA-1566948     6
## R-HSA-2022090     6
## R-HSA-1650814     6
## R-HSA-1474290     6
## R-HSA-166663      4
## R-HSA-8957275     6
## R-HSA-166658      5
## R-HSA-3000170     4
## R-HSA-8874081     4
## R-HSA-3560782     4
## R-HSA-8875878     4
## R-HSA-419037      4
## R-HSA-9006934     9
## R-HSA-977606      4
## R-HSA-3000480     3
## R-HSA-186797      4
## R-HSA-3560783     3
## R-HSA-3560801     3
## R-HSA-4420332     3
## R-HSA-3000171     4
## R-HSA-375165      4
## R-HSA-1971475     3
## R-HSA-6806834     4
## R-HSA-76009       3
## R-HSA-2173782     3
## R-HSA-1793185     3
## R-HSA-2022923     2
## R-HSA-1630316     4
## R-HSA-430116      2
## R-HSA-1638091     3
## R-HSA-198933      4
## R-HSA-166786      2
## R-HSA-2024101     2
## R-HSA-3781865     4
## R-HSA-2214320     2
## R-HSA-75892       2
## R-HSA-2243919     2
## R-HSA-2022870     2
## R-HSA-6785807     3
## R-HSA-1592389     2
## R-HSA-114604      2
## R-HSA-76002       4
## R-HSA-202733      3
## R-HSA-71387       4
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_13"
## [1] "ACTB"   "B2M"    "CCL5"   "CD74"   "GNLY"   "HLA-A"  "HLA-B"  "NKG7"  
## [9] "TMSB10"
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                                   Description GeneRatio
## GO:0050998 GO:0050998                 nitric-oxide synthase binding       2/8
## GO:0042605 GO:0042605                       peptide antigen binding       2/8
## GO:0042277 GO:0042277                               peptide binding       3/8
## GO:0033218 GO:0033218                                 amide binding       3/8
## GO:0003823 GO:0003823                               antigen binding       2/8
## GO:0030957 GO:0030957                           Tat protein binding       1/8
## GO:0099186 GO:0099186         structural constituent of postsynapse       1/8
## GO:0016004 GO:0016004              phospholipase activator activity       1/8
## GO:0060229 GO:0060229                     lipase activator activity       1/8
## GO:0023026 GO:0023026          MHC class II protein complex binding       1/8
## GO:0098918 GO:0098918             structural constituent of synapse       1/8
## GO:0030296 GO:0030296    protein tyrosine kinase activator activity       1/8
## GO:0044183 GO:0044183   protein binding involved in protein folding       1/8
## GO:0023023 GO:0023023                   MHC protein complex binding       1/8
## GO:0004435 GO:0004435 phosphatidylinositol phospholipase C activity       1/8
## GO:0003785 GO:0003785                         actin monomer binding       1/8
## GO:0004629 GO:0004629                      phospholipase C activity       1/8
## GO:0048019 GO:0048019                  receptor antagonist activity       1/8
## GO:0042056 GO:0042056                      chemoattractant activity       1/8
## GO:0042287 GO:0042287                           MHC protein binding       1/8
## GO:0030547 GO:0030547                   receptor inhibitor activity       1/8
## GO:0019894 GO:0019894                               kinesin binding       1/8
## GO:0048020 GO:0048020                CCR chemokine receptor binding       1/8
## GO:0048156 GO:0048156                           tau protein binding       1/8
## GO:0008009 GO:0008009                            chemokine activity       1/8
## GO:0031492 GO:0031492                       nucleosomal DNA binding       1/8
## GO:0043621 GO:0043621                      protein self-association       1/8
##              BgRatio       pvalue     p.adjust       qvalue        geneID Count
## GO:0050998  14/17697 1.622842e-05 0.0008114212 0.0002220732        60/972     2
## GO:0042605  31/17697 8.260728e-05 0.0020651819 0.0005652077     3105/3106     2
## GO:0042277 295/17697 2.413230e-04 0.0040220492 0.0011007714 972/3105/3106     3
## GO:0033218 356/17697 4.193453e-04 0.0052418161 0.0014346023 972/3105/3106     3
## GO:0003823 160/17697 2.194675e-03 0.0219467511 0.0060064793     3105/3106     2
## GO:0030957  10/17697 4.512501e-03 0.0338303721 0.0092588387            60     1
## GO:0099186  11/17697 4.962769e-03 0.0338303721 0.0092588387            60     1
## GO:0016004  12/17697 5.412860e-03 0.0338303721 0.0092588387          6352     1
## GO:0060229  14/17697 6.312506e-03 0.0348210917 0.0095299830          6352     1
## GO:0023026  16/17697 7.211440e-03 0.0348210917 0.0095299830           972     1
## GO:0098918  17/17697 7.660640e-03 0.0348210917 0.0095299830            60     1
## GO:0030296  19/17697 8.558507e-03 0.0356604461 0.0097597010          6352     1
## GO:0044183  23/17697 1.035211e-02 0.0370297569 0.0101344598           972     1
## GO:0023023  25/17697 1.124784e-02 0.0370297569 0.0101344598           972     1
## GO:0004435  26/17697 1.169545e-02 0.0370297569 0.0101344598          6352     1
## GO:0003785  28/17697 1.259012e-02 0.0370297569 0.0101344598          9168     1
## GO:0004629  28/17697 1.259012e-02 0.0370297569 0.0101344598          6352     1
## GO:0048019  33/17697 1.482370e-02 0.0411769346 0.0112694768          6352     1
## GO:0042056  38/17697 1.705285e-02 0.0419078166 0.0114695077          6352     1
## GO:0042287  40/17697 1.794328e-02 0.0419078166 0.0114695077           972     1
## GO:0030547  41/17697 1.838823e-02 0.0419078166 0.0114695077          6352     1
## GO:0019894  42/17697 1.883300e-02 0.0419078166 0.0114695077            60     1
## GO:0048020  43/17697 1.927760e-02 0.0419078166 0.0114695077          6352     1
## GO:0048156  45/17697 2.016626e-02 0.0420130377 0.0114983051            60     1
## GO:0008009  49/17697 2.194147e-02 0.0438829391 0.0120100675          6352     1
## GO:0031492  55/17697 2.459901e-02 0.0463728123 0.0126915065            60     1
## GO:0043621  56/17697 2.504132e-02 0.0463728123 0.0126915065          6352     1
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1236977 R-HSA-1236977
## R-HSA-983170   R-HSA-983170
## R-HSA-1236974 R-HSA-1236974
## R-HSA-877300   R-HSA-877300
## R-HSA-1236975 R-HSA-1236975
## R-HSA-198933   R-HSA-198933
## R-HSA-913531   R-HSA-913531
## R-HSA-909733   R-HSA-909733
## R-HSA-983169   R-HSA-983169
##                                                                              Description
## R-HSA-1236977                                                 Endosomal/Vacuolar pathway
## R-HSA-983170  Antigen Presentation: Folding, assembly and peptide loading of class I MHC
## R-HSA-1236974                                                       ER-Phagosome pathway
## R-HSA-877300                                                  Interferon gamma signaling
## R-HSA-1236975                                      Antigen processing-Cross presentation
## R-HSA-198933    Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-913531                                                        Interferon Signaling
## R-HSA-909733                                             Interferon alpha/beta signaling
## R-HSA-983169                      Class I MHC mediated antigen processing & presentation
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1236977       3/7  11/10654 2.859621e-08 2.516467e-06 1.324456e-06
## R-HSA-983170        3/7  25/10654 3.970436e-07 1.746992e-05 9.194695e-06
## R-HSA-1236974       3/7  83/10654 1.560343e-05 4.577006e-04 2.408950e-04
## R-HSA-877300        3/7  92/10654 2.127201e-05 4.666826e-04 2.456224e-04
## R-HSA-1236975       3/7  99/10654 2.651606e-05 4.666826e-04 2.456224e-04
## R-HSA-198933        3/7 132/10654 6.274825e-05 9.203077e-04 4.843725e-04
## R-HSA-913531        3/7 199/10654 2.125815e-04 2.672453e-03 1.406554e-03
## R-HSA-909733        2/7  69/10654 8.501123e-04 9.351236e-03 4.921703e-03
## R-HSA-983169        3/7 371/10654 1.320576e-03 1.291230e-02 6.795947e-03
##                      geneID Count
## R-HSA-1236977 567/3105/3106     3
## R-HSA-983170  567/3105/3106     3
## R-HSA-1236974 567/3105/3106     3
## R-HSA-877300  567/3105/3106     3
## R-HSA-1236975 567/3105/3106     3
## R-HSA-198933  567/3105/3106     3
## R-HSA-913531  567/3105/3106     3
## R-HSA-909733      3105/3106     2
## R-HSA-983169  567/3105/3106     3
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## Warning in clusterProfiler::bitr(d$gene_name, fromType = "SYMBOL", toType =
## "ENTREZID", : 2.78% of input gene IDs are fail to map...
## [1] "cluster_14"
##   [1] "A2M"      "ACKR1"    "ACTA2"    "ACTG1"    "ACTN4"    "ADGRL4"  
##   [7] "AEBP1"    "APOD"     "APP"      "AQP1"     "B2M"      "BST2"    
##  [13] "C1R"      "C1S"      "C2orf40"  "C3"       "CALD1"    "CAVIN1"  
##  [19] "CD34"     "CD44"     "CD59"     "CD74"     "CD93"     "CLDN5"   
##  [25] "COL14A1"  "CRIP2"    "CST3"     "CTGF"     "CTSC"     "CXCL12"  
##  [31] "CXCL14"   "EEF1B2"   "EEF1D"    "EGFL7"    "ENG"      "EPAS1"   
##  [37] "FAU"      "FKBP1A"   "FLNA"     "FN1"      "FOS"      "FOXP1"   
##  [43] "FXYD5"    "GGT5"     "GIMAP4"   "GNAI2"    "GSN"      "H3F3B"   
##  [49] "HLA-A"    "HLA-B"    "HLA-C"    "HLA-DMA"  "HLA-DPA1" "HLA-DPB1"
##  [55] "HLA-DQB1" "HLA-DRA"  "HLA-DRB1" "HLA-E"    "HSPB1"    "IFI16"   
##  [61] "IFI27"    "IFITM2"   "IFITM3"   "IGFBP4"   "IGFBP5"   "IGFBP7"  
##  [67] "KCTD12"   "KLF2"     "LIFR"     "LMOD1"    "LRRFIP1"  "LY6E"    
##  [73] "MGP"      "MYH9"     "NOP53"    "NOTCH3"   "NR2F2"    "PECAM1"  
##  [79] "PFDN5"    "PLAT"     "PLVAP"    "PRRX1"    "PTMS"     "RACK1"   
##  [85] "RAMP2"    "RAMP3"    "RNASE1"   "S100A4"   "S100A6"   "SAMHD1"  
##  [91] "SPARCL1"  "STEAP4"   "SYNE2"    "SYNPO2"   "TAGLN"    "TCF4"    
##  [97] "TGFBR2"   "TIMP3"    "TM4SF1"   "TMSB10"   "TMSB4X"   "TNFSF10" 
## [103] "TSPAN7"   "TXNIP"    "UBA52"    "VWF"      "ZFP36L1"  "ZFP36L2" 
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0042605 GO:0042605
## GO:0042277 GO:0042277
## GO:0033218 GO:0033218
## GO:0003823 GO:0003823
## GO:0003779 GO:0003779
## GO:0023026 GO:0023026
## GO:0005518 GO:0005518
## GO:0061134 GO:0061134
## GO:0023023 GO:0023023
## GO:0019838 GO:0019838
## GO:0032395 GO:0032395
## GO:0034713 GO:0034713
## GO:0050839 GO:0050839
## GO:0016504 GO:0016504
## GO:0005523 GO:0005523
## GO:0019955 GO:0019955
## GO:0004857 GO:0004857
## GO:0005201 GO:0005201
## GO:0004866 GO:0004866
## GO:0005520 GO:0005520
## GO:0030414 GO:0030414
## GO:0061135 GO:0061135
## GO:0045296 GO:0045296
## GO:0002020 GO:0002020
## GO:0005178 GO:0005178
## GO:0051015 GO:0051015
## GO:0046332 GO:0046332
## GO:0005126 GO:0005126
## GO:0031994 GO:0031994
## GO:0048185 GO:0048185
## GO:0005160 GO:0005160
## GO:0008191 GO:0008191
## GO:0048306 GO:0048306
## GO:0016505 GO:0016505
## GO:0003746 GO:0003746
## GO:0001848 GO:0001848
##                                                           Description GeneRatio
## GO:0042605                                    peptide antigen binding     9/102
## GO:0042277                                            peptide binding    13/102
## GO:0033218                                              amide binding    13/102
## GO:0003823                                            antigen binding     9/102
## GO:0003779                                              actin binding    13/102
## GO:0023026                       MHC class II protein complex binding     4/102
## GO:0005518                                           collagen binding     6/102
## GO:0061134                               peptidase regulator activity     9/102
## GO:0023023                                MHC protein complex binding     4/102
## GO:0019838                                      growth factor binding     7/102
## GO:0032395                             MHC class II receptor activity     3/102
## GO:0034713    type I transforming growth factor beta receptor binding     3/102
## GO:0050839                             cell adhesion molecule binding    12/102
## GO:0016504                               peptidase activator activity     4/102
## GO:0005523                                        tropomyosin binding     3/102
## GO:0019955                                           cytokine binding     6/102
## GO:0004857                                  enzyme inhibitor activity     9/102
## GO:0005201                extracellular matrix structural constituent     6/102
## GO:0004866                           endopeptidase inhibitor activity     6/102
## GO:0005520                         insulin-like growth factor binding     3/102
## GO:0030414                               peptidase inhibitor activity     6/102
## GO:0061135                           endopeptidase regulator activity     6/102
## GO:0045296                                           cadherin binding     8/102
## GO:0002020                                           protease binding     5/102
## GO:0005178                                           integrin binding     5/102
## GO:0051015                                     actin filament binding     6/102
## GO:0046332                                               SMAD binding     4/102
## GO:0005126                                  cytokine receptor binding     7/102
## GO:0031994                       insulin-like growth factor I binding     2/102
## GO:0048185                                            activin binding     2/102
## GO:0005160           transforming growth factor beta receptor binding     3/102
## GO:0008191                    metalloendopeptidase inhibitor activity     2/102
## GO:0048306                          calcium-dependent protein binding     3/102
## GO:0016505 peptidase activator activity involved in apoptotic process     2/102
## GO:0003746                     translation elongation factor activity     2/102
## GO:0001848                                         complement binding     2/102
##              BgRatio       pvalue     p.adjust       qvalue
## GO:0042605  31/17697 8.884548e-14 2.398828e-11 1.945248e-11
## GO:0042277 295/17697 1.463811e-08 1.976145e-06 1.602488e-06
## GO:0033218 356/17697 1.323549e-07 1.191194e-05 9.659587e-06
## GO:0003823 160/17697 3.599187e-07 2.429451e-05 1.970081e-05
## GO:0003779 431/17697 1.158673e-06 6.256833e-05 5.073767e-05
## GO:0023026  16/17697 1.794941e-06 8.077235e-05 6.549961e-05
## GO:0005518  67/17697 2.373086e-06 9.153333e-05 7.422586e-05
## GO:0061134 219/17697 4.883831e-06 1.648293e-04 1.336627e-04
## GO:0023023  25/17697 1.198809e-05 3.596428e-04 2.916402e-04
## GO:0019838 137/17697 1.430767e-05 3.863072e-04 3.132627e-04
## GO:0032395  10/17697 2.166220e-05 5.317086e-04 4.311711e-04
## GO:0034713  11/17697 2.966074e-05 6.212546e-04 5.037854e-04
## GO:0050839 499/17697 2.991226e-05 6.212546e-04 5.037854e-04
## GO:0016504  38/17697 6.604305e-05 1.273687e-03 1.032854e-03
## GO:0005523  15/17697 8.043052e-05 1.447749e-03 1.174003e-03
## GO:0019955 128/17697 9.718037e-05 1.639919e-03 1.329837e-03
## GO:0004857 375/17697 3.164793e-04 5.026436e-03 4.076018e-03
## GO:0005201 163/17697 3.616957e-04 5.425435e-03 4.399573e-03
## GO:0004866 175/17697 5.274435e-04 7.403680e-03 6.003764e-03
## GO:0005520  28/17697 5.484208e-04 7.403680e-03 6.003764e-03
## GO:0030414 182/17697 6.483435e-04 7.712459e-03 6.254158e-03
## GO:0061135 182/17697 6.483435e-04 7.712459e-03 6.254158e-03
## GO:0045296 331/17697 6.569873e-04 7.712459e-03 6.254158e-03
## GO:0002020 128/17697 8.705061e-04 9.793194e-03 7.941459e-03
## GO:0005178 132/17697 9.994949e-04 1.043900e-02 8.465152e-03
## GO:0051015 198/17697 1.005237e-03 1.043900e-02 8.465152e-03
## GO:0046332  80/17697 1.176003e-03 1.176003e-02 9.536397e-03
## GO:0005126 286/17697 1.336294e-03 1.288569e-02 1.044922e-02
## GO:0031994  12/17697 2.090882e-03 1.946683e-02 1.578597e-02
## GO:0048185  14/17697 2.861299e-03 2.575169e-02 2.088246e-02
## GO:0005160  51/17697 3.167501e-03 2.758791e-02 2.237148e-02
## GO:0008191  16/17697 3.744917e-03 3.159774e-02 2.562312e-02
## GO:0048306  61/17697 5.251524e-03 4.190406e-02 3.398068e-02
## GO:0016505  19/17697 5.276807e-03 4.190406e-02 3.398068e-02
## GO:0003746  20/17697 5.841192e-03 4.506063e-02 3.654039e-02
## GO:0001848  21/17697 6.431921e-03 4.823941e-02 3.911812e-02
##                                                                        geneID
## GO:0042605                       3105/3106/3107/3113/3115/3119/3122/3123/3133
## GO:0042277  972/1471/3105/3106/3107/3113/3115/3119/3122/3123/3133/10266/10268
## GO:0033218  972/1471/3105/3106/3107/3113/3115/3119/3122/3123/3133/10266/10268
## GO:0003823                       3105/3106/3107/3113/3115/3119/3122/3123/3133
## GO:0003779 81/800/2316/53827/2934/25802/4627/6275/23224/171024/6876/9168/7114
## GO:0023026                                                 972/3108/3122/3123
## GO:0005518                                        165/960/7373/2335/8404/7450
## GO:0061134                            2/351/684/718/1471/1075/2335/10399/7078
## GO:0023023                                                 972/3108/3122/3123
## GO:0019838                                    2/2022/3487/3488/3490/3977/7048
## GO:0032395                                                     3113/3119/3122
## GO:0034713                                                     2022/2280/7048
## GO:0050839         81/800/6387/1936/2316/2335/53827/9208/4627/4854/10399/7450
## GO:0016504                                                351/1075/2335/10399
## GO:0005523                                                     800/25802/6277
## GO:0019955                                          2/2532/972/2022/3977/7048
## GO:0004857                           2/351/684/718/1471/3315/10399/7078/10628
## GO:0005201                                       165/7373/2335/3490/4256/7450
## GO:0004866                                            2/351/684/718/1471/7078
## GO:0005520                                                     3487/3488/3490
## GO:0030414                                            2/351/684/718/1471/7078
## GO:0061135                                            2/351/684/718/1471/7078
## GO:0045296                           800/1936/2316/53827/9208/4627/4854/10399
## GO:0002020                                              2/1471/2335/7078/7450
## GO:0005178                                             81/6387/2335/4627/7450
## GO:0051015                                       81/2316/2934/4627/23224/6876
## GO:0046332                                                2280/2316/2353/7048
## GO:0005126                                 6387/9547/2022/2280/3977/7048/8743
## GO:0031994                                                          3487/3488
## GO:0048185                                                          2022/2280
## GO:0005160                                                     2022/2280/7048
## GO:0008191                                                           684/7078
## GO:0048306                                                        2/6275/6277
## GO:0016505                                                         1075/10399
## GO:0003746                                                          1933/1936
## GO:0001848                                                          966/22918
##            Count
## GO:0042605     9
## GO:0042277    13
## GO:0033218    13
## GO:0003823     9
## GO:0003779    13
## GO:0023026     4
## GO:0005518     6
## GO:0061134     9
## GO:0023023     4
## GO:0019838     7
## GO:0032395     3
## GO:0034713     3
## GO:0050839    12
## GO:0016504     4
## GO:0005523     3
## GO:0019955     6
## GO:0004857     9
## GO:0005201     6
## GO:0004866     6
## GO:0005520     3
## GO:0030414     6
## GO:0061135     6
## GO:0045296     8
## GO:0002020     5
## GO:0005178     5
## GO:0051015     6
## GO:0046332     4
## GO:0005126     7
## GO:0031994     2
## GO:0048185     2
## GO:0005160     3
## GO:0008191     2
## GO:0048306     3
## GO:0016505     2
## GO:0003746     2
## GO:0001848     2
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-913531   R-HSA-913531
## R-HSA-877300   R-HSA-877300
## R-HSA-909733   R-HSA-909733
## R-HSA-1236977 R-HSA-1236977
## R-HSA-202430   R-HSA-202430
## R-HSA-114608   R-HSA-114608
## R-HSA-202427   R-HSA-202427
## R-HSA-389948   R-HSA-389948
## R-HSA-76005     R-HSA-76005
## R-HSA-983170   R-HSA-983170
## R-HSA-8957275 R-HSA-8957275
## R-HSA-381426   R-HSA-381426
## R-HSA-202433   R-HSA-202433
## R-HSA-76002     R-HSA-76002
## R-HSA-1236974 R-HSA-1236974
## R-HSA-2132295 R-HSA-2132295
## R-HSA-198933   R-HSA-198933
## R-HSA-202424   R-HSA-202424
## R-HSA-1236975 R-HSA-1236975
## R-HSA-388841   R-HSA-388841
## R-HSA-2173791 R-HSA-2173791
## R-HSA-6798695 R-HSA-6798695
## R-HSA-202403   R-HSA-202403
## R-HSA-977606   R-HSA-977606
## R-HSA-166663   R-HSA-166663
## R-HSA-166658   R-HSA-166658
## R-HSA-977225   R-HSA-977225
## R-HSA-2173789 R-HSA-2173789
## R-HSA-419812   R-HSA-419812
## R-HSA-6802948 R-HSA-6802948
##                                                                                                                               Description
## R-HSA-913531                                                                                                         Interferon Signaling
## R-HSA-877300                                                                                                   Interferon gamma signaling
## R-HSA-909733                                                                                              Interferon alpha/beta signaling
## R-HSA-1236977                                                                                                  Endosomal/Vacuolar pathway
## R-HSA-202430                                                                             Translocation of ZAP-70 to Immunological synapse
## R-HSA-114608                                                                                                      Platelet degranulation 
## R-HSA-202427                                                                                   Phosphorylation of CD3 and TCR zeta chains
## R-HSA-389948                                                                                                               PD-1 signaling
## R-HSA-76005                                                                                  Response to elevated platelet cytosolic Ca2+
## R-HSA-983170                                                   Antigen Presentation: Folding, assembly and peptide loading of class I MHC
## R-HSA-8957275                                                                                  Post-translational protein phosphorylation
## R-HSA-381426  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
## R-HSA-202433                                                                                     Generation of second messenger molecules
## R-HSA-76002                                                                                Platelet activation, signaling and aggregation
## R-HSA-1236974                                                                                                        ER-Phagosome pathway
## R-HSA-2132295                                                                                           MHC class II antigen presentation
## R-HSA-198933                                                     Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-202424                                                                                                     Downstream TCR signaling
## R-HSA-1236975                                                                                       Antigen processing-Cross presentation
## R-HSA-388841                                                                                             Costimulation by the CD28 family
## R-HSA-2173791                                                   TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
## R-HSA-6798695                                                                                                    Neutrophil degranulation
## R-HSA-202403                                                                                                                TCR signaling
## R-HSA-977606                                                                                             Regulation of Complement cascade
## R-HSA-166663                                                                                             Initial triggering of complement
## R-HSA-166658                                                                                                           Complement cascade
## R-HSA-977225                                                                                                      Amyloid fiber formation
## R-HSA-2173789                                                                                 TGF-beta receptor signaling activates SMADs
## R-HSA-419812                                                                                             Calcitonin-like ligand receptors
## R-HSA-6802948                                                                              Signaling by high-kinase activity BRAF mutants
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-913531      18/80 199/10654 4.555126e-15 2.541760e-12 2.220025e-12
## R-HSA-877300      11/80  92/10654 6.940172e-11 1.936308e-08 1.691210e-08
## R-HSA-909733       9/80  69/10654 1.884905e-09 3.505924e-07 3.062144e-07
## R-HSA-1236977      5/80  11/10654 9.381387e-09 1.308704e-06 1.143048e-06
## R-HSA-202430       5/80  19/10654 2.252663e-07 2.513971e-05 2.195753e-05
## R-HSA-114608       9/80 129/10654 4.745985e-07 3.995630e-05 3.489863e-05
## R-HSA-202427       5/80  22/10654 5.012439e-07 3.995630e-05 3.489863e-05
## R-HSA-389948       5/80  23/10654 6.367250e-07 4.064199e-05 3.549753e-05
## R-HSA-76005        9/80 134/10654 6.555160e-07 4.064199e-05 3.549753e-05
## R-HSA-983170       5/80  25/10654 9.936085e-07 5.544335e-05 4.842534e-05
## R-HSA-8957275      8/80 108/10654 1.359570e-06 6.896727e-05 6.023740e-05
## R-HSA-381426       8/80 125/10654 4.099809e-06 1.817701e-04 1.587617e-04
## R-HSA-202433       5/80  33/10654 4.234788e-06 1.817701e-04 1.587617e-04
## R-HSA-76002       10/80 262/10654 2.465542e-05 9.826948e-04 8.583054e-04
## R-HSA-1236974      6/80  83/10654 3.532910e-05 1.269890e-03 1.109147e-03
## R-HSA-2132295      7/80 123/10654 3.641260e-05 1.269890e-03 1.109147e-03
## R-HSA-198933       7/80 132/10654 5.724084e-05 1.878846e-03 1.641022e-03
## R-HSA-202424       6/80  98/10654 9.011388e-05 2.793530e-03 2.439926e-03
## R-HSA-1236975      6/80  99/10654 9.535895e-05 2.800542e-03 2.446050e-03
## R-HSA-388841       5/80  70/10654 1.738547e-04 4.850545e-03 4.236564e-03
## R-HSA-2173791      3/80  16/10654 2.127857e-04 5.654020e-03 4.938335e-03
## R-HSA-6798695     12/80 480/10654 2.247466e-04 5.700392e-03 4.978837e-03
## R-HSA-202403       6/80 119/10654 2.622198e-04 6.361680e-03 5.556419e-03
## R-HSA-977606       4/80  47/10654 4.113985e-04 9.565016e-03 8.354277e-03
## R-HSA-166663       3/80  23/10654 6.479216e-04 1.446161e-02 1.263106e-02
## R-HSA-166658       4/80  58/10654 9.193237e-04 1.973010e-02 1.723267e-02
## R-HSA-977225       5/80 109/10654 1.336524e-03 2.762149e-02 2.412517e-02
## R-HSA-2173789      3/80  32/10654 1.728566e-03 3.444786e-02 3.008745e-02
## R-HSA-419812       2/80  10/10654 2.409767e-03 4.529566e-02 3.956214e-02
## R-HSA-6802948      3/80  36/10654 2.435251e-03 4.529566e-02 3.956214e-02
##                                                                                                  geneID
## R-HSA-913531  567/684/960/2316/3105/3106/3107/3113/3115/3119/3122/3123/3133/3429/10581/10410/25939/7311
## R-HSA-877300                                       567/960/3105/3106/3107/3113/3115/3119/3122/3123/3133
## R-HSA-909733                                             684/3105/3106/3107/3133/3429/10581/10410/25939
## R-HSA-1236977                                                                   567/3105/3106/3107/3133
## R-HSA-202430                                                                   3113/3115/3119/3122/3123
## R-HSA-114608                                                     2/81/351/2316/2335/5175/7078/7114/7450
## R-HSA-202427                                                                   3113/3115/3119/3122/3123
## R-HSA-389948                                                                   3113/3115/3119/3122/3123
## R-HSA-76005                                                      2/81/351/2316/2335/5175/7078/7114/7450
## R-HSA-983170                                                                    567/3105/3106/3107/3133
## R-HSA-8957275                                                     351/718/1471/2335/3487/3488/3490/8404
## R-HSA-381426                                                      351/718/1471/2335/3487/3488/3490/8404
## R-HSA-202433                                                                   3113/3115/3119/3122/3123
## R-HSA-76002                                                 2/81/351/2316/2335/2771/5175/7078/7114/7450
## R-HSA-1236974                                                              567/3105/3106/3107/3133/7311
## R-HSA-2132295                                                         972/1075/3113/3115/3119/3122/3123
## R-HSA-198933                                                            567/718/947/3105/3106/3107/3133
## R-HSA-202424                                                              3113/3115/3119/3122/3123/7311
## R-HSA-1236975                                                              567/3105/3106/3107/3133/7311
## R-HSA-388841                                                                   3113/3115/3119/3122/3123
## R-HSA-2173791                                                                            2280/7048/7311
## R-HSA-6798695                                   567/684/718/960/966/22918/1471/1075/2934/3106/3107/5175
## R-HSA-202403                                                              3113/3115/3119/3122/3123/7311
## R-HSA-977606                                                                            715/716/718/966
## R-HSA-166663                                                                                715/716/718
## R-HSA-166658                                                                            715/716/718/966
## R-HSA-977225                                                                     351/567/1471/2934/7311
## R-HSA-2173789                                                                            2280/7048/7311
## R-HSA-419812                                                                                10266/10268
## R-HSA-6802948                                                                              71/2335/7450
##               Count
## R-HSA-913531     18
## R-HSA-877300     11
## R-HSA-909733      9
## R-HSA-1236977     5
## R-HSA-202430      5
## R-HSA-114608      9
## R-HSA-202427      5
## R-HSA-389948      5
## R-HSA-76005       9
## R-HSA-983170      5
## R-HSA-8957275     8
## R-HSA-381426      8
## R-HSA-202433      5
## R-HSA-76002      10
## R-HSA-1236974     6
## R-HSA-2132295     7
## R-HSA-198933      7
## R-HSA-202424      6
## R-HSA-1236975     6
## R-HSA-388841      5
## R-HSA-2173791     3
## R-HSA-6798695    12
## R-HSA-202403      6
## R-HSA-977606      4
## R-HSA-166663      3
## R-HSA-166658      4
## R-HSA-977225      5
## R-HSA-2173789     3
## R-HSA-419812      2
## R-HSA-6802948     3
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_15"
## [1] "B2M"    "LYZ"    "S100A8" "S100A9"
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                                          Description
## GO:0050786 GO:0050786                                RAGE receptor binding
## GO:0035325 GO:0035325                           Toll-like receptor binding
## GO:0036041 GO:0036041                        long-chain fatty acid binding
## GO:1901567 GO:1901567                        fatty acid derivative binding
## GO:0005504 GO:0005504                                   fatty acid binding
## GO:0033293 GO:0033293                          monocarboxylic acid binding
## GO:0031406 GO:0031406                              carboxylic acid binding
## GO:0043177 GO:0043177                                 organic acid binding
## GO:0008017 GO:0008017                                  microtubule binding
## GO:0015631 GO:0015631                                      tubulin binding
## GO:0061783 GO:0061783                     peptidoglycan muralytic activity
## GO:0016209 GO:0016209                                 antioxidant activity
## GO:0004553 GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds
## GO:0016798 GO:0016798         hydrolase activity, acting on glycosyl bonds
##            GeneRatio   BgRatio       pvalue     p.adjust qvalue    geneID Count
## GO:0050786       2/4  11/17697 2.106079e-06 1.625780e-05     NA 6279/6280     2
## GO:0035325       2/4  12/17697 2.527104e-06 1.625780e-05     NA 6279/6280     2
## GO:0036041       2/4  14/17697 3.483815e-06 1.625780e-05     NA 6279/6280     2
## GO:1901567       2/4  28/17697 1.445596e-05 5.059587e-05     NA 6279/6280     2
## GO:0005504       2/4  34/17697 2.144478e-05 6.004538e-05     NA 6279/6280     2
## GO:0033293       2/4  64/17697 7.688931e-05 1.794084e-04     NA 6279/6280     2
## GO:0031406       2/4 193/17697 6.997852e-04 1.380807e-03     NA 6279/6280     2
## GO:0043177       2/4 205/17697 7.890327e-04 1.380807e-03     NA 6279/6280     2
## GO:0008017       2/4 246/17697 1.133602e-03 1.763380e-03     NA 6279/6280     2
## GO:0015631       2/4 336/17697 2.102664e-03 2.943729e-03     NA 6279/6280     2
## GO:0061783       1/4  13/17697 2.935364e-03 3.735917e-03     NA      4069     1
## GO:0016209       1/4  86/17697 1.929871e-02 2.251516e-02     NA      6280     1
## GO:0004553       1/4  94/17697 2.107963e-02 2.270114e-02     NA      4069     1
## GO:0016798       1/4 117/17697 2.618626e-02 2.618626e-02     NA      4069     1
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-6803157 R-HSA-6803157
## R-HSA-6798695 R-HSA-6798695
## R-HSA-5686938 R-HSA-5686938
## R-HSA-5668599 R-HSA-5668599
## R-HSA-977225   R-HSA-977225
## R-HSA-168898   R-HSA-168898
## R-HSA-1236977 R-HSA-1236977
## R-HSA-195258   R-HSA-195258
## R-HSA-164938   R-HSA-164938
## R-HSA-983170   R-HSA-983170
## R-HSA-164952   R-HSA-164952
## R-HSA-194315   R-HSA-194315
## R-HSA-2424491 R-HSA-2424491
## R-HSA-2172127 R-HSA-2172127
## R-HSA-1236974 R-HSA-1236974
## R-HSA-877300   R-HSA-877300
## R-HSA-1236975 R-HSA-1236975
##                                                                                                  Description
## R-HSA-6803157                                                                         Antimicrobial peptides
## R-HSA-6798695                                                                       Neutrophil degranulation
## R-HSA-5686938                                                         Regulation of TLR by endogenous ligand
## R-HSA-5668599                                                            RHO GTPases Activate NADPH Oxidases
## R-HSA-977225                                                                         Amyloid fiber formation
## R-HSA-168898                                                                     Toll-like Receptor Cascades
## R-HSA-1236977                                                                     Endosomal/Vacuolar pathway
## R-HSA-195258                                                                            RHO GTPase Effectors
## R-HSA-164938  Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
## R-HSA-983170                      Antigen Presentation: Folding, assembly and peptide loading of class I MHC
## R-HSA-164952                                   The role of Nef in HIV-1 replication and disease pathogenesis
## R-HSA-194315                                                                        Signaling by Rho GTPases
## R-HSA-2424491                                                                                DAP12 signaling
## R-HSA-2172127                                                                             DAP12 interactions
## R-HSA-1236974                                                                           ER-Phagosome pathway
## R-HSA-877300                                                                      Interferon gamma signaling
## R-HSA-1236975                                                          Antigen processing-Cross presentation
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-6803157       3/4  97/10654 2.907546e-06 0.0000468182 8.570837e-06
## R-HSA-6798695       4/4 480/10654 4.071148e-06 0.0000468182 8.570837e-06
## R-HSA-5686938       2/4  19/10654 1.804131e-05 0.0001383167 2.532114e-05
## R-HSA-5668599       2/4  24/10654 2.910107e-05 0.0001673312 3.063271e-05
## R-HSA-977225        2/4 109/10654 6.140205e-04 0.0028244945 5.170699e-04
## R-HSA-168898        2/4 155/10654 1.237845e-03 0.0047450743 8.686635e-04
## R-HSA-1236977       1/4  11/10654 4.124092e-03 0.0135505893 2.480657e-03
## R-HSA-195258        2/4 327/10654 5.408852e-03 0.0155504494 2.846764e-03
## R-HSA-164938        1/4  20/10654 7.488851e-03 0.0191381744 3.503556e-03
## R-HSA-983170        1/4  25/10654 9.354473e-03 0.0197626051 3.617868e-03
## R-HSA-164952        1/4  27/10654 1.009998e-02 0.0197626051 3.617868e-03
## R-HSA-194315        2/4 455/10654 1.031092e-02 0.0197626051 3.617868e-03
## R-HSA-2424491       1/4  30/10654 1.121746e-02 0.0198462814 3.633187e-03
## R-HSA-2172127       1/4  43/10654 1.604894e-02 0.0263661192 4.826750e-03
## R-HSA-1236974       1/4  83/10654 3.080403e-02 0.0472328423 8.646745e-03
## R-HSA-877300        1/4  92/10654 3.410092e-02 0.0490200740 8.973927e-03
## R-HSA-1236975       1/4  99/10654 3.665935e-02 0.0495979451 9.079715e-03
##                           geneID Count
## R-HSA-6803157     4069/6279/6280     3
## R-HSA-6798695 567/4069/6279/6280     4
## R-HSA-5686938          6279/6280     2
## R-HSA-5668599          6279/6280     2
## R-HSA-977225            567/4069     2
## R-HSA-168898           6279/6280     2
## R-HSA-1236977                567     1
## R-HSA-195258           6279/6280     2
## R-HSA-164938                 567     1
## R-HSA-983170                 567     1
## R-HSA-164952                 567     1
## R-HSA-194315           6279/6280     2
## R-HSA-2424491                567     1
## R-HSA-2172127                567     1
## R-HSA-1236974                567     1
## R-HSA-877300                 567     1
## R-HSA-1236975                567     1
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_16"
##  [1] "A2M"      "ACTB"     "ACTG1"    "AIF1"     "B2M"      "C1QA"    
##  [7] "CD74"     "CST3"     "CTSB"     "CTSS"     "GRN"      "HLA-A"   
## [13] "HLA-B"    "HLA-C"    "HLA-DPA1" "HLA-DPB1" "HLA-DQB1" "HLA-DRA" 
## [19] "HLA-DRB1" "HLA-DRB5" "HLA-E"    "LCP1"     "LYZ"      "PSAP"    
## [25] "RNASE1"   "SAMHD1"   "SH3BGRL3" "TMSB10"   "TMSB4X"   "TYROBP"  
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                           Description GeneRatio   BgRatio
## GO:0042605 GO:0042605               peptide antigen binding     10/30  31/17697
## GO:0033218 GO:0033218                         amide binding     14/30 356/17697
## GO:0042277 GO:0042277                       peptide binding     13/30 295/17697
## GO:0003823 GO:0003823                       antigen binding     10/30 160/17697
## GO:0032395 GO:0032395        MHC class II receptor activity      3/30  10/17697
## GO:0023026 GO:0023026  MHC class II protein complex binding      3/30  16/17697
## GO:0023023 GO:0023023           MHC protein complex binding      3/30  25/17697
## GO:0099186 GO:0099186 structural constituent of postsynapse      2/30  11/17697
## GO:0050998 GO:0050998         nitric-oxide synthase binding      2/30  14/17697
## GO:0001540 GO:0001540                  amyloid-beta binding      3/30  78/17697
## GO:0098918 GO:0098918     structural constituent of synapse      2/30  17/17697
## GO:0001871 GO:0001871                       pattern binding      2/30  25/17697
## GO:0030247 GO:0030247                polysaccharide binding      2/30  25/17697
## GO:0003785 GO:0003785                 actin monomer binding      2/30  28/17697
## GO:0002020 GO:0002020                      protease binding      3/30 128/17697
## GO:0043394 GO:0043394                  proteoglycan binding      2/30  36/17697
## GO:0042287 GO:0042287                   MHC protein binding      2/30  40/17697
## GO:0005518 GO:0005518                      collagen binding      2/30  67/17697
## GO:0003779 GO:0003779                         actin binding      4/30 431/17697
##                  pvalue     p.adjust       qvalue
## GO:0042605 1.574614e-21 1.432899e-19 7.955944e-20
## GO:0033218 1.498224e-16 6.816920e-15 3.784987e-15
## GO:0042277 5.477842e-16 1.661612e-14 9.225839e-15
## GO:0003823 7.066848e-14 1.607708e-12 8.926545e-13
## GO:0032395 5.233019e-07 9.524095e-06 5.288104e-06
## GO:0023026 2.425359e-06 3.678462e-05 2.042408e-05
## GO:0023023 9.859218e-06 1.281698e-04 7.116428e-05
## GO:0099186 1.513503e-04 1.721609e-03 9.558965e-04
## GO:0050998 2.496250e-04 2.523986e-03 1.401403e-03
## GO:0001540 3.069341e-04 2.793100e-03 1.550825e-03
## GO:0098918 3.718878e-04 3.076527e-03 1.708193e-03
## GO:0001871 8.134547e-04 5.694183e-03 3.161605e-03
## GO:0030247 8.134547e-04 5.694183e-03 3.161605e-03
## GO:0003785 1.021720e-03 6.641177e-03 3.687409e-03
## GO:0002020 1.300906e-03 7.892164e-03 4.382000e-03
## GO:0043394 1.688586e-03 9.603833e-03 5.332377e-03
## GO:0042287 2.081851e-03 1.114402e-02 6.187544e-03
## GO:0005518 5.736207e-03 2.758055e-02 1.531367e-02
## GO:0003779 5.758577e-03 2.758055e-02 1.531367e-02
##                                                                         geneID
## GO:0042605                   3105/3106/3107/3113/3115/3119/3122/3123/3127/3133
## GO:0033218 712/972/1471/3105/3106/3107/3113/3115/3119/3122/3123/3127/3133/5660
## GO:0042277      712/972/1471/3105/3106/3107/3113/3115/3119/3122/3123/3127/3133
## GO:0003823                   3105/3106/3107/3113/3115/3119/3122/3123/3127/3133
## GO:0032395                                                      3113/3119/3122
## GO:0023026                                                       972/3122/3123
## GO:0023023                                                       972/3122/3123
## GO:0099186                                                               60/71
## GO:0050998                                                              60/972
## GO:0001540                                                        712/972/1471
## GO:0098918                                                               60/71
## GO:0001871                                                           3122/3123
## GO:0030247                                                           3122/3123
## GO:0003785                                                           9168/7114
## GO:0002020                                                         2/1471/5660
## GO:0043394                                                           1508/1520
## GO:0042287                                                            972/3133
## GO:0005518                                                           1508/1520
## GO:0003779                                                  199/3936/9168/7114
##            Count
## GO:0042605    10
## GO:0033218    14
## GO:0042277    13
## GO:0003823    10
## GO:0032395     3
## GO:0023026     3
## GO:0023023     3
## GO:0099186     2
## GO:0050998     2
## GO:0001540     3
## GO:0098918     2
## GO:0001871     2
## GO:0030247     2
## GO:0003785     2
## GO:0002020     3
## GO:0043394     2
## GO:0042287     2
## GO:0005518     2
## GO:0003779     4
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-877300   R-HSA-877300
## R-HSA-913531   R-HSA-913531
## R-HSA-1236977 R-HSA-1236977
## R-HSA-202430   R-HSA-202430
## R-HSA-202427   R-HSA-202427
## R-HSA-2132295 R-HSA-2132295
## R-HSA-389948   R-HSA-389948
## R-HSA-202433   R-HSA-202433
## R-HSA-983170   R-HSA-983170
## R-HSA-388841   R-HSA-388841
## R-HSA-202424   R-HSA-202424
## R-HSA-6798695 R-HSA-6798695
## R-HSA-1236975 R-HSA-1236975
## R-HSA-202403   R-HSA-202403
## R-HSA-909733   R-HSA-909733
## R-HSA-198933   R-HSA-198933
## R-HSA-1236974 R-HSA-1236974
## R-HSA-2424491 R-HSA-2424491
## R-HSA-2172127 R-HSA-2172127
## R-HSA-983169   R-HSA-983169
## R-HSA-196025   R-HSA-196025
## R-HSA-190873   R-HSA-190873
## R-HSA-1679131 R-HSA-1679131
## R-HSA-446353   R-HSA-446353
## R-HSA-977225   R-HSA-977225
## R-HSA-445095   R-HSA-445095
## R-HSA-5626467 R-HSA-5626467
## R-HSA-418990   R-HSA-418990
## R-HSA-5663213 R-HSA-5663213
## R-HSA-6802948 R-HSA-6802948
## R-HSA-114608   R-HSA-114608
## R-HSA-1500931 R-HSA-1500931
## R-HSA-5674135 R-HSA-5674135
## R-HSA-76005     R-HSA-76005
## R-HSA-3928662 R-HSA-3928662
## R-HSA-1474228 R-HSA-1474228
## R-HSA-190828   R-HSA-190828
## R-HSA-437239   R-HSA-437239
## R-HSA-6802946 R-HSA-6802946
## R-HSA-6802949 R-HSA-6802949
## R-HSA-6802955 R-HSA-6802955
## R-HSA-9649948 R-HSA-9649948
## R-HSA-157858   R-HSA-157858
## R-HSA-3928665 R-HSA-3928665
## R-HSA-2022090 R-HSA-2022090
## R-HSA-2029482 R-HSA-2029482
## R-HSA-421270   R-HSA-421270
## R-HSA-6802952 R-HSA-6802952
## R-HSA-6802957 R-HSA-6802957
## R-HSA-1445148 R-HSA-1445148
## R-HSA-2029480 R-HSA-2029480
##                                                                              Description
## R-HSA-877300                                                  Interferon gamma signaling
## R-HSA-913531                                                        Interferon Signaling
## R-HSA-1236977                                                 Endosomal/Vacuolar pathway
## R-HSA-202430                            Translocation of ZAP-70 to Immunological synapse
## R-HSA-202427                                  Phosphorylation of CD3 and TCR zeta chains
## R-HSA-2132295                                          MHC class II antigen presentation
## R-HSA-389948                                                              PD-1 signaling
## R-HSA-202433                                    Generation of second messenger molecules
## R-HSA-983170  Antigen Presentation: Folding, assembly and peptide loading of class I MHC
## R-HSA-388841                                            Costimulation by the CD28 family
## R-HSA-202424                                                    Downstream TCR signaling
## R-HSA-6798695                                                   Neutrophil degranulation
## R-HSA-1236975                                      Antigen processing-Cross presentation
## R-HSA-202403                                                               TCR signaling
## R-HSA-909733                                             Interferon alpha/beta signaling
## R-HSA-198933    Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-1236974                                                       ER-Phagosome pathway
## R-HSA-2424491                                                            DAP12 signaling
## R-HSA-2172127                                                         DAP12 interactions
## R-HSA-983169                      Class I MHC mediated antigen processing & presentation
## R-HSA-196025                                          Formation of annular gap junctions
## R-HSA-190873                                                    Gap junction degradation
## R-HSA-1679131                                Trafficking and processing of endosomal TLR
## R-HSA-446353                                      Cell-extracellular matrix interactions
## R-HSA-977225                                                     Amyloid fiber formation
## R-HSA-445095                                         Interaction between L1 and Ankyrins
## R-HSA-5626467                                                RHO GTPases activate IQGAPs
## R-HSA-418990                                             Adherens junctions interactions
## R-HSA-5663213                                       RHO GTPases Activate WASPs and WAVEs
## R-HSA-6802948                             Signaling by high-kinase activity BRAF mutants
## R-HSA-114608                                                     Platelet degranulation 
## R-HSA-1500931                                                    Cell-Cell communication
## R-HSA-5674135                                                  MAP2K and MAPK activation
## R-HSA-76005                                 Response to elevated platelet cytosolic Ca2+
## R-HSA-3928662                                            EPHB-mediated forward signaling
## R-HSA-1474228                                    Degradation of the extracellular matrix
## R-HSA-190828                                                    Gap junction trafficking
## R-HSA-437239                                                     Recycling pathway of L1
## R-HSA-6802946                         Signaling by moderate kinase activity BRAF mutants
## R-HSA-6802949                                                   Signaling by RAS mutants
## R-HSA-6802955            Paradoxical activation of RAF signaling by kinase inactive BRAF
## R-HSA-9649948                                        Signaling downstream of RAS mutants
## R-HSA-157858                                     Gap junction trafficking and regulation
## R-HSA-3928665                                     EPH-ephrin mediated repulsion of cells
## R-HSA-2022090               Assembly of collagen fibrils and other multimeric structures
## R-HSA-2029482                  Regulation of actin dynamics for phagocytic cup formation
## R-HSA-421270                                             Cell-cell junction organization
## R-HSA-6802952                                          Signaling by BRAF and RAF fusions
## R-HSA-6802957                                                   Oncogenic MAPK signaling
## R-HSA-1445148                     Translocation of SLC2A4 (GLUT4) to the plasma membrane
## R-HSA-2029480                             Fcgamma receptor (FCGR) dependent phagocytosis
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-877300      11/27  92/10654 1.252282e-16 1.590398e-14 8.040970e-15
## R-HSA-913531      12/27 199/10654 1.759968e-14 1.117580e-12 5.650425e-13
## R-HSA-1236977      6/27  11/10654 6.685625e-14 2.830248e-12 1.430958e-12
## R-HSA-202430       6/27  19/10654 3.873480e-12 1.229830e-10 6.217954e-11
## R-HSA-202427       6/27  22/10654 1.059810e-11 2.257797e-10 1.141530e-10
## R-HSA-2132295      9/27 123/10654 1.066676e-11 2.257797e-10 1.141530e-10
## R-HSA-389948       6/27  23/10654 1.431436e-11 2.597033e-10 1.313046e-10
## R-HSA-202433       6/27  33/10654 1.544165e-10 2.451361e-09 1.239395e-09
## R-HSA-983170       5/27  25/10654 3.626013e-09 5.116707e-08 2.586980e-08
## R-HSA-388841       6/27  70/10654 1.716861e-08 2.180413e-07 1.102405e-07
## R-HSA-202424       6/27  98/10654 1.314324e-07 1.364512e-06 6.898899e-07
## R-HSA-6798695     10/27 480/10654 1.325804e-07 1.364512e-06 6.898899e-07
## R-HSA-1236975      6/27  99/10654 1.396744e-07 1.364512e-06 6.898899e-07
## R-HSA-202403       6/27 119/10654 4.180917e-07 3.792689e-06 1.917563e-06
## R-HSA-909733       5/27  69/10654 7.109353e-07 6.019252e-06 3.043302e-06
## R-HSA-198933       6/27 132/10654 7.715844e-07 6.124451e-06 3.096490e-06
## R-HSA-1236974      5/27  83/10654 1.792813e-06 1.339337e-05 6.771616e-06
## R-HSA-2424491      3/27  30/10654 5.630719e-05 3.972785e-04 2.008619e-04
## R-HSA-2172127      3/27  43/10654 1.674369e-04 1.119183e-03 5.658531e-04
## R-HSA-983169       6/27 371/10654 2.722946e-04 1.729071e-03 8.742089e-04
## R-HSA-196025       2/27  11/10654 3.354268e-04 2.028534e-03 1.025616e-03
## R-HSA-190873       2/27  12/10654 4.018831e-04 2.319962e-03 1.172960e-03
## R-HSA-1679131      2/27  13/10654 4.742106e-04 2.618467e-03 1.323883e-03
## R-HSA-446353       2/27  18/10654 9.229398e-04 4.883890e-03 2.469269e-03
## R-HSA-977225       3/27 109/10654 2.548266e-03 1.294519e-02 6.545019e-03
## R-HSA-445095       2/27  31/10654 2.748647e-03 1.342608e-02 6.788156e-03
## R-HSA-5626467      2/27  32/10654 2.927319e-03 1.376924e-02 6.961656e-03
## R-HSA-418990       2/27  33/10654 3.111322e-03 1.411207e-02 7.134986e-03
## R-HSA-5663213      2/27  36/10654 3.695045e-03 1.564236e-02 7.908692e-03
## R-HSA-6802948      2/27  36/10654 3.695045e-03 1.564236e-02 7.908692e-03
## R-HSA-114608       3/27 129/10654 4.101985e-03 1.627975e-02 8.230957e-03
## R-HSA-1500931      3/27 129/10654 4.101985e-03 1.627975e-02 8.230957e-03
## R-HSA-5674135      2/27  40/10654 4.546381e-03 1.704484e-02 8.617783e-03
## R-HSA-76005        3/27 134/10654 4.563187e-03 1.704484e-02 8.617783e-03
## R-HSA-3928662      2/27  42/10654 5.002891e-03 1.815335e-02 9.178235e-03
## R-HSA-1474228      3/27 140/10654 5.156767e-03 1.819193e-02 9.197743e-03
## R-HSA-190828       2/27  47/10654 6.232490e-03 1.884586e-02 9.528368e-03
## R-HSA-437239       2/27  47/10654 6.232490e-03 1.884586e-02 9.528368e-03
## R-HSA-6802946      2/27  47/10654 6.232490e-03 1.884586e-02 9.528368e-03
## R-HSA-6802949      2/27  47/10654 6.232490e-03 1.884586e-02 9.528368e-03
## R-HSA-6802955      2/27  47/10654 6.232490e-03 1.884586e-02 9.528368e-03
## R-HSA-9649948      2/27  47/10654 6.232490e-03 1.884586e-02 9.528368e-03
## R-HSA-157858       2/27  49/10654 6.759134e-03 1.996302e-02 1.009320e-02
## R-HSA-3928665      2/27  51/10654 7.305368e-03 2.108595e-02 1.066094e-02
## R-HSA-2022090      2/27  61/10654 1.032356e-02 2.850199e-02 1.441046e-02
## R-HSA-2029482      2/27  61/10654 1.032356e-02 2.850199e-02 1.441046e-02
## R-HSA-421270       2/27  64/10654 1.131995e-02 3.058794e-02 1.546510e-02
## R-HSA-6802952      2/27  67/10654 1.235717e-02 3.269502e-02 1.653043e-02
## R-HSA-6802957      2/27  71/10654 1.380257e-02 3.577400e-02 1.808715e-02
## R-HSA-1445148      2/27  72/10654 1.417491e-02 3.600428e-02 1.820357e-02
## R-HSA-2029480      2/27  86/10654 1.983449e-02 4.939176e-02 2.497221e-02
##                                                                    geneID Count
## R-HSA-877300        567/3105/3106/3107/3113/3115/3119/3122/3123/3127/3133    11
## R-HSA-913531  567/3105/3106/3107/3113/3115/3119/3122/3123/3127/3133/25939    12
## R-HSA-1236977                                567/1520/3105/3106/3107/3133     6
## R-HSA-202430                                3113/3115/3119/3122/3123/3127     6
## R-HSA-202427                                3113/3115/3119/3122/3123/3127     6
## R-HSA-2132295                 972/1508/1520/3113/3115/3119/3122/3123/3127     9
## R-HSA-389948                                3113/3115/3119/3122/3123/3127     6
## R-HSA-202433                                3113/3115/3119/3122/3123/3127     6
## R-HSA-983170                                      567/3105/3106/3107/3133     5
## R-HSA-388841                                3113/3115/3119/3122/3123/3127     6
## R-HSA-202424                                3113/3115/3119/3122/3123/3127     6
## R-HSA-6798695            567/1471/1508/1520/2896/3106/3107/4069/5660/7305    10
## R-HSA-1236975                                567/1520/3105/3106/3107/3133     6
## R-HSA-202403                                3113/3115/3119/3122/3123/3127     6
## R-HSA-909733                                    3105/3106/3107/3133/25939     5
## R-HSA-198933                                 567/3105/3106/3107/3133/7305     6
## R-HSA-1236974                                     567/3105/3106/3107/3133     5
## R-HSA-2424491                                               567/3133/7305     3
## R-HSA-2172127                                               567/3133/7305     3
## R-HSA-983169                                 567/1520/3105/3106/3107/3133     6
## R-HSA-196025                                                        60/71     2
## R-HSA-190873                                                        60/71     2
## R-HSA-1679131                                                   1508/1520     2
## R-HSA-446353                                                        60/71     2
## R-HSA-977225                                                567/1471/4069     3
## R-HSA-445095                                                        60/71     2
## R-HSA-5626467                                                       60/71     2
## R-HSA-418990                                                        60/71     2
## R-HSA-5663213                                                       60/71     2
## R-HSA-6802948                                                       60/71     2
## R-HSA-114608                                                  2/5660/7114     3
## R-HSA-1500931                                                  60/71/7305     3
## R-HSA-5674135                                                       60/71     2
## R-HSA-76005                                                   2/5660/7114     3
## R-HSA-3928662                                                       60/71     2
## R-HSA-1474228                                                 2/1508/1520     3
## R-HSA-190828                                                        60/71     2
## R-HSA-437239                                                        60/71     2
## R-HSA-6802946                                                       60/71     2
## R-HSA-6802949                                                       60/71     2
## R-HSA-6802955                                                       60/71     2
## R-HSA-9649948                                                       60/71     2
## R-HSA-157858                                                        60/71     2
## R-HSA-3928665                                                       60/71     2
## R-HSA-2022090                                                   1508/1520     2
## R-HSA-2029482                                                       60/71     2
## R-HSA-421270                                                        60/71     2
## R-HSA-6802952                                                       60/71     2
## R-HSA-6802957                                                       60/71     2
## R-HSA-1445148                                                       60/71     2
## R-HSA-2029480                                                       60/71     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## Warning in clusterProfiler::bitr(d$gene_name, fromType = "SYMBOL", toType =
## "ENTREZID", : 2.38% of input gene IDs are fail to map...
## [1] "cluster_17"
##  [1] "A2M"      "ACTA2"    "ACTG1"    "ACTN4"    "APOD"     "B2M"     
##  [7] "BGN"      "C12orf57" "CALD1"    "CFH"      "CLDN5"    "CRIP2"   
## [13] "CXCL12"   "DCN"      "EPAS1"    "FLNA"     "GJA4"     "GSN"     
## [19] "H3F3B"    "HLA-A"    "HLA-B"    "HLA-C"    "HLA-E"    "ID1"     
## [25] "IFI27"    "IFITM3"   "IGFBP3"   "IGFBP7"   "KCTD12"   "LBH"     
## [31] "MGP"      "NOTCH3"   "NR2F2"    "RERGL"    "ROCK1"    "SEMA3G"  
## [37] "SPARCL1"  "TAGLN"    "TIMP3"    "TM4SF1"   "TMSB10"   "TSC22D1" 
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0042605 GO:0042605
## GO:0050840 GO:0050840
## GO:0003779 GO:0003779
## GO:0003823 GO:0003823
## GO:0005201 GO:0005201
## GO:0051015 GO:0051015
## GO:0030021 GO:0030021
## GO:0005520 GO:0005520
## GO:0047485 GO:0047485
## GO:0019838 GO:0019838
## GO:0042277 GO:0042277
##                                                                              Description
## GO:0042605                                                       peptide antigen binding
## GO:0050840                                                  extracellular matrix binding
## GO:0003779                                                                 actin binding
## GO:0003823                                                               antigen binding
## GO:0005201                                   extracellular matrix structural constituent
## GO:0051015                                                        actin filament binding
## GO:0030021 extracellular matrix structural constituent conferring compression resistance
## GO:0005520                                            insulin-like growth factor binding
## GO:0047485                                                    protein N-terminus binding
## GO:0019838                                                         growth factor binding
## GO:0042277                                                               peptide binding
##            GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## GO:0042605      4/41  31/17697 7.454880e-07 8.573112e-05 5.963904e-05
## GO:0050840      3/41  57/17697 3.096109e-04 1.238829e-02 8.617940e-03
## GO:0003779      6/41 431/17697 4.400233e-04 1.238829e-02 8.617940e-03
## GO:0003823      4/41 160/17697 5.022056e-04 1.238829e-02 8.617940e-03
## GO:0005201      4/41 163/17697 5.386213e-04 1.238829e-02 8.617940e-03
## GO:0051015      4/41 198/17697 1.113585e-03 1.929862e-02 1.342513e-02
## GO:0030021      2/41  22/17697 1.174698e-03 1.929862e-02 1.342513e-02
## GO:0005520      2/41  28/17697 1.905403e-03 2.611337e-02 1.816582e-02
## GO:0047485      3/41 109/17697 2.043655e-03 2.611337e-02 1.816582e-02
## GO:0019838      3/41 137/17697 3.902284e-03 4.487626e-02 3.121827e-02
## GO:0042277      4/41 295/17697 4.716882e-03 4.931285e-02 3.430459e-02
##                                geneID Count
## GO:0042605        3105/3106/3107/3133     4
## GO:0050840              633/1634/8404     3
## GO:0003779 81/800/2316/2934/6876/9168     6
## GO:0003823        3105/3106/3107/3133     4
## GO:0005201         633/1634/3490/4256     4
## GO:0051015          81/2316/2934/6876     4
## GO:0030021                   633/1634     2
## GO:0005520                  3486/3490     2
## GO:0047485               81/1634/3397     3
## GO:0019838                2/3486/3490     3
## GO:0042277        3105/3106/3107/3133     4
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-1236977 R-HSA-1236977
## R-HSA-983170   R-HSA-983170
## R-HSA-909733   R-HSA-909733
## R-HSA-913531   R-HSA-913531
## R-HSA-1236974 R-HSA-1236974
## R-HSA-877300   R-HSA-877300
## R-HSA-1236975 R-HSA-1236975
## R-HSA-198933   R-HSA-198933
## R-HSA-2022923 R-HSA-2022923
## R-HSA-114608   R-HSA-114608
## R-HSA-1500931 R-HSA-1500931
## R-HSA-76005     R-HSA-76005
## R-HSA-2024101 R-HSA-2024101
## R-HSA-446353   R-HSA-446353
## R-HSA-2022870 R-HSA-2022870
## R-HSA-3560783 R-HSA-3560783
## R-HSA-3560801 R-HSA-3560801
## R-HSA-4420332 R-HSA-4420332
## R-HSA-446728   R-HSA-446728
## R-HSA-1971475 R-HSA-1971475
## R-HSA-2424491 R-HSA-2424491
## R-HSA-8957275 R-HSA-8957275
## R-HSA-983169   R-HSA-983169
## R-HSA-111465   R-HSA-111465
## R-HSA-381426   R-HSA-381426
## R-HSA-445355   R-HSA-445355
## R-HSA-3560782 R-HSA-3560782
## R-HSA-76002     R-HSA-76002
## R-HSA-3928662 R-HSA-3928662
## R-HSA-2172127 R-HSA-2172127
## R-HSA-3781865 R-HSA-3781865
## R-HSA-190828   R-HSA-190828
## R-HSA-157858   R-HSA-157858
## R-HSA-1793185 R-HSA-1793185
## R-HSA-75153     R-HSA-75153
## R-HSA-6798695 R-HSA-6798695
## R-HSA-1638091 R-HSA-1638091
##                                                                                                                               Description
## R-HSA-1236977                                                                                                  Endosomal/Vacuolar pathway
## R-HSA-983170                                                   Antigen Presentation: Folding, assembly and peptide loading of class I MHC
## R-HSA-909733                                                                                              Interferon alpha/beta signaling
## R-HSA-913531                                                                                                         Interferon Signaling
## R-HSA-1236974                                                                                                        ER-Phagosome pathway
## R-HSA-877300                                                                                                   Interferon gamma signaling
## R-HSA-1236975                                                                                       Antigen processing-Cross presentation
## R-HSA-198933                                                     Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-2022923                                                                                               Dermatan sulfate biosynthesis
## R-HSA-114608                                                                                                      Platelet degranulation 
## R-HSA-1500931                                                                                                     Cell-Cell communication
## R-HSA-76005                                                                                  Response to elevated platelet cytosolic Ca2+
## R-HSA-2024101                                                                                                           CS/DS degradation
## R-HSA-446353                                                                                       Cell-extracellular matrix interactions
## R-HSA-2022870                                                                                            Chondroitin sulfate biosynthesis
## R-HSA-3560783                                                                                Defective B4GALT7 causes EDS, progeroid type
## R-HSA-3560801                                                                                             Defective B3GAT3 causes JDSSDHD
## R-HSA-4420332                                                                                  Defective B3GALT6 causes EDSP2 and SEMDJL1
## R-HSA-446728                                                                                                   Cell junction organization
## R-HSA-1971475                                                             A tetrasaccharide linker sequence is required for GAG synthesis
## R-HSA-2424491                                                                                                             DAP12 signaling
## R-HSA-8957275                                                                                  Post-translational protein phosphorylation
## R-HSA-983169                                                                       Class I MHC mediated antigen processing & presentation
## R-HSA-111465                                                                                      Apoptotic cleavage of cellular proteins
## R-HSA-381426  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
## R-HSA-445355                                                                                                    Smooth Muscle Contraction
## R-HSA-3560782                                                                       Diseases associated with glycosaminoglycan metabolism
## R-HSA-76002                                                                                Platelet activation, signaling and aggregation
## R-HSA-3928662                                                                                             EPHB-mediated forward signaling
## R-HSA-2172127                                                                                                          DAP12 interactions
## R-HSA-3781865                                                                                                   Diseases of glycosylation
## R-HSA-190828                                                                                                     Gap junction trafficking
## R-HSA-157858                                                                                      Gap junction trafficking and regulation
## R-HSA-1793185                                                                             Chondroitin sulfate/dermatan sulfate metabolism
## R-HSA-75153                                                                                                     Apoptotic execution phase
## R-HSA-6798695                                                                                                    Neutrophil degranulation
## R-HSA-1638091                                                                                 Heparan sulfate/heparin (HS-GAG) metabolism
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-1236977      5/30  11/10654 5.693738e-11 8.540607e-09 5.813606e-09
## R-HSA-983170       5/30  25/10654 6.370670e-09 4.778002e-07 3.252395e-07
## R-HSA-909733       6/30  69/10654 3.106340e-08 1.553170e-06 1.057245e-06
## R-HSA-913531       8/30 199/10654 5.296007e-08 1.986003e-06 1.351876e-06
## R-HSA-1236974      5/30  83/10654 3.107236e-06 9.321709e-05 6.345304e-05
## R-HSA-877300       5/30  92/10654 5.170778e-06 1.292695e-04 8.799395e-05
## R-HSA-1236975      5/30  99/10654 7.417776e-06 1.589523e-04 1.081991e-04
## R-HSA-198933       5/30 132/10654 3.006760e-05 5.637674e-04 3.837575e-04
## R-HSA-2022923      2/30  11/10654 4.149979e-04 6.006265e-03 4.088475e-03
## R-HSA-114608       4/30 129/10654 4.404594e-04 6.006265e-03 4.088475e-03
## R-HSA-1500931      4/30 129/10654 4.404594e-04 6.006265e-03 4.088475e-03
## R-HSA-76005        4/30 134/10654 5.087357e-04 6.359196e-03 4.328716e-03
## R-HSA-2024101      2/30  14/10654 6.830347e-04 7.881170e-03 5.364726e-03
## R-HSA-446353       2/30  18/10654 1.140387e-03 1.176016e-02 8.005163e-03
## R-HSA-2022870      2/30  20/10654 1.411220e-03 1.176016e-02 8.005163e-03
## R-HSA-3560783      2/30  20/10654 1.411220e-03 1.176016e-02 8.005163e-03
## R-HSA-3560801      2/30  20/10654 1.411220e-03 1.176016e-02 8.005163e-03
## R-HSA-4420332      2/30  20/10654 1.411220e-03 1.176016e-02 8.005163e-03
## R-HSA-446728       3/30  91/10654 2.071222e-03 1.635175e-02 1.113067e-02
## R-HSA-1971475      2/30  26/10654 2.388736e-03 1.791552e-02 1.219512e-02
## R-HSA-2424491      2/30  30/10654 3.174964e-03 2.258068e-02 1.537071e-02
## R-HSA-8957275      3/30 108/10654 3.370481e-03 2.258068e-02 1.537071e-02
## R-HSA-983169       5/30 371/10654 3.462371e-03 2.258068e-02 1.537071e-02
## R-HSA-111465       2/30  38/10654 5.059878e-03 3.047945e-02 2.074741e-02
## R-HSA-381426       3/30 125/10654 5.079908e-03 3.047945e-02 2.074741e-02
## R-HSA-445355       2/30  40/10654 5.594539e-03 3.172147e-02 2.159286e-02
## R-HSA-3560782      2/30  41/10654 5.871191e-03 3.172147e-02 2.159286e-02
## R-HSA-76002        4/30 262/10654 5.921342e-03 3.172147e-02 2.159286e-02
## R-HSA-3928662      2/30  42/10654 6.154012e-03 3.183110e-02 2.166748e-02
## R-HSA-2172127      2/30  43/10654 6.442966e-03 3.221483e-02 2.192869e-02
## R-HSA-3781865      3/30 143/10654 7.373919e-03 3.568025e-02 2.428761e-02
## R-HSA-190828       2/30  47/10654 7.659432e-03 3.590359e-02 2.443963e-02
## R-HSA-157858       2/30  49/10654 8.303578e-03 3.774354e-02 2.569209e-02
## R-HSA-1793185      2/30  50/10654 8.634511e-03 3.809343e-02 2.593027e-02
## R-HSA-75153        2/30  52/10654 9.313931e-03 3.991685e-02 2.717147e-02
## R-HSA-6798695      5/30 480/10654 1.018677e-02 4.206667e-02 2.863485e-02
## R-HSA-1638091      2/30  55/10654 1.037644e-02 4.206667e-02 2.863485e-02
##                                                geneID Count
## R-HSA-1236977                 567/3105/3106/3107/3133     5
## R-HSA-983170                  567/3105/3106/3107/3133     5
## R-HSA-909733           3105/3106/3107/3133/3429/10410     6
## R-HSA-913531  567/2316/3105/3106/3107/3133/3429/10410     8
## R-HSA-1236974                 567/3105/3106/3107/3133     5
## R-HSA-877300                  567/3105/3106/3107/3133     5
## R-HSA-1236975                 567/3105/3106/3107/3133     5
## R-HSA-198933                  567/3105/3106/3107/3133     5
## R-HSA-2022923                                633/1634     2
## R-HSA-114608                           2/81/2316/7078     4
## R-HSA-1500931                         71/81/7122/2316     4
## R-HSA-76005                            2/81/2316/7078     4
## R-HSA-2024101                                633/1634     2
## R-HSA-446353                                  71/2316     2
## R-HSA-2022870                                633/1634     2
## R-HSA-3560783                                633/1634     2
## R-HSA-3560801                                633/1634     2
## R-HSA-4420332                                633/1634     2
## R-HSA-446728                             71/7122/2316     3
## R-HSA-1971475                                633/1634     2
## R-HSA-2424491                                567/3133     2
## R-HSA-8957275                          3486/3490/8404     3
## R-HSA-983169                  567/3105/3106/3107/3133     5
## R-HSA-111465                                2934/6093     2
## R-HSA-381426                           3486/3490/8404     3
## R-HSA-445355                                   59/800     2
## R-HSA-3560782                                633/1634     2
## R-HSA-76002                            2/81/2316/7078     4
## R-HSA-3928662                                 71/6093     2
## R-HSA-2172127                                567/3133     2
## R-HSA-3781865                           633/1634/4854     3
## R-HSA-190828                                  71/2701     2
## R-HSA-157858                                  71/2701     2
## R-HSA-1793185                                633/1634     2
## R-HSA-75153                                 2934/6093     2
## R-HSA-6798695                 567/2934/3106/3107/6093     5
## R-HSA-1638091                                633/1634     2
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_18"
## [1] "IGHG1"  "IGHG3"  "IGHG4"  "IGKC"   "JCHAIN" "SCD"   
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                       Description GeneRatio   BgRatio
## GO:0034987 GO:0034987   immunoglobulin receptor binding       5/6  76/17697
## GO:0003823 GO:0003823                   antigen binding       5/6 160/17697
## GO:0042834 GO:0042834             peptidoglycan binding       1/6  17/17697
## GO:0019865 GO:0019865            immunoglobulin binding       1/6  24/17697
## GO:0031210 GO:0031210       phosphatidylcholine binding       1/6  27/17697
## GO:0050997 GO:0050997 quaternary ammonium group binding       1/6  27/17697
##                  pvalue     p.adjust       qvalue                   geneID
## GO:0034987 7.641973e-12 1.069876e-10 4.826510e-11 3500/3502/3503/3514/3512
## GO:0003823 3.379983e-10 2.365988e-09 1.067363e-09 3500/3502/3503/3514/3512
## GO:0042834 5.750675e-03 2.128124e-02 9.600561e-03                     3512
## GO:0019865 8.110577e-03 2.128124e-02 9.600561e-03                     3512
## GO:0031210 9.120533e-03 2.128124e-02 9.600561e-03                     3512
## GO:0050997 9.120533e-03 2.128124e-02 9.600561e-03                     3512
##            Count
## GO:0034987     5
## GO:0003823     5
## GO:0042834     1
## GO:0019865     1
## GO:0031210     1
## GO:0050997     1
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-2168880 R-HSA-2168880
## R-HSA-75105     R-HSA-75105
## R-HSA-2173782 R-HSA-2173782
## R-HSA-2426168 R-HSA-2426168
## R-HSA-9024446 R-HSA-9024446
## R-HSA-1655829 R-HSA-1655829
## R-HSA-202733   R-HSA-202733
## R-HSA-8957322 R-HSA-8957322
## R-HSA-8978868 R-HSA-8978868
##                                                           Description GeneRatio
## R-HSA-2168880                          Scavenging of heme from plasma       1/2
## R-HSA-75105                               Fatty acyl-CoA biosynthesis       1/2
## R-HSA-2173782    Binding and Uptake of Ligands by Scavenger Receptors       1/2
## R-HSA-2426168          Activation of gene expression by SREBF (SREBP)       1/2
## R-HSA-9024446                      NR1H2 and NR1H3-mediated signaling       1/2
## R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)       1/2
## R-HSA-202733           Cell surface interactions at the vascular wall       1/2
## R-HSA-8957322                                  Metabolism of steroids       1/2
## R-HSA-8978868                                   Fatty acid metabolism       1/2
##                 BgRatio      pvalue   p.adjust      qvalue geneID Count
## R-HSA-2168880  13/10654 0.002439023 0.01716432 0.001806771   3512     1
## R-HSA-75105    37/10654 0.006934012 0.01716432 0.001806771   6319     1
## R-HSA-2173782  42/10654 0.007869190 0.01716432 0.001806771   3512     1
## R-HSA-2426168  42/10654 0.007869190 0.01716432 0.001806771   6319     1
## R-HSA-9024446  47/10654 0.008803928 0.01716432 0.001806771   6319     1
## R-HSA-1655829  55/10654 0.010298593 0.01716432 0.001806771   6319     1
## R-HSA-202733  137/10654 0.025553877 0.03518325 0.003703500   3512     1
## R-HSA-8957322 151/10654 0.028146596 0.03518325 0.003703500   6319     1
## R-HSA-8978868 177/10654 0.032952483 0.03661387 0.003854092   6319     1
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_19"
##  [1] "ACTA2"   "ACTG2"   "AEBP1"   "CALD1"   "CNN1"    "CSRP1"   "DES"    
##  [8] "FLNA"    "IGFBP5"  "IGFBP7"  "MGP"     "MYH11"   "MYLK"    "SPARCL1"
## [15] "SYNPO2"  "TAGLN"   "TPM1"    "TPM2"   
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID                                 Description GeneRatio
## GO:0003779 GO:0003779                               actin binding      9/18
## GO:0008307 GO:0008307            structural constituent of muscle      4/18
## GO:0051015 GO:0051015                      actin filament binding      5/18
## GO:0005516 GO:0005516                          calmodulin binding      5/18
## GO:0005520 GO:0005520          insulin-like growth factor binding      2/18
## GO:0005201 GO:0005201 extracellular matrix structural constituent      3/18
## GO:0042805 GO:0042805                             actinin binding      2/18
## GO:0005518 GO:0005518                            collagen binding      2/18
## GO:0005200 GO:0005200      structural constituent of cytoskeleton      2/18
## GO:0019838 GO:0019838                       growth factor binding      2/18
## GO:0031994 GO:0031994        insulin-like growth factor I binding      1/18
## GO:0031005 GO:0031005                             filamin binding      1/18
## GO:0005523 GO:0005523                         tropomyosin binding      1/18
## GO:0017160 GO:0017160                          Ral GTPase binding      1/18
##              BgRatio       pvalue     p.adjust       qvalue
## GO:0003779 431/17697 1.110705e-10 4.887102e-09 2.689076e-09
## GO:0008307  46/17697 1.190163e-07 2.618359e-06 1.440724e-06
## GO:0051015 198/17697 1.268697e-06 1.466433e-05 8.068891e-06
## GO:0005516 200/17697 1.333121e-06 1.466433e-05 8.068891e-06
## GO:0005520  28/17697 3.636073e-04 3.199744e-03 1.760625e-03
## GO:0005201 163/17697 5.654459e-04 4.146603e-03 2.281624e-03
## GO:0042805  46/17697 9.848561e-04 6.190524e-03 3.406269e-03
## GO:0005518  67/17697 2.077456e-03 1.142601e-02 6.287037e-03
## GO:0005200 102/17697 4.739084e-03 2.316886e-02 1.274841e-02
## GO:0019838 137/17697 8.392735e-03 3.692803e-02 2.031925e-02
## GO:0031994  12/17697 1.214116e-02 4.762883e-02 2.620725e-02
## GO:0031005  13/17697 1.314662e-02 4.762883e-02 2.620725e-02
## GO:0005523  15/17697 1.515463e-02 4.762883e-02 2.620725e-02
## GO:0017160  15/17697 1.515463e-02 4.762883e-02 2.620725e-02
##                                                   geneID Count
## GO:0003779 800/1264/2316/4629/4638/171024/6876/7168/7169     9
## GO:0008307                           1465/4629/7168/7169     4
## GO:0051015                      2316/4629/6876/7168/7169     5
## GO:0005516                        165/800/1264/4629/4638     5
## GO:0005520                                     3488/3490     2
## GO:0005201                                 165/3490/4256     3
## GO:0042805                                   1465/171024     2
## GO:0005518                                      165/8404     2
## GO:0005200                                     1674/7168     2
## GO:0019838                                     3488/3490     2
## GO:0031994                                          3488     1
## GO:0031005                                        171024     1
## GO:0005523                                           800     1
## GO:0017160                                          2316     1
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-445355   R-HSA-445355
## R-HSA-397014   R-HSA-397014
## R-HSA-5627123 R-HSA-5627123
## R-HSA-390522   R-HSA-390522
## R-HSA-8957275 R-HSA-8957275
## R-HSA-381426   R-HSA-381426
## R-HSA-195258   R-HSA-195258
##                                                                                                                               Description
## R-HSA-445355                                                                                                    Smooth Muscle Contraction
## R-HSA-397014                                                                                                           Muscle contraction
## R-HSA-5627123                                                                                                   RHO GTPases activate PAKs
## R-HSA-390522                                                                                                  Striated Muscle Contraction
## R-HSA-8957275                                                                                  Post-translational protein phosphorylation
## R-HSA-381426  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
## R-HSA-195258                                                                                                         RHO GTPase Effectors
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-445355       7/13  40/10654 1.020156e-14 3.366516e-13 1.718158e-13
## R-HSA-397014       8/13 209/10654 2.270674e-11 3.746613e-10 1.912147e-10
## R-HSA-5627123      3/13  24/10654 2.830648e-06 3.113713e-05 1.589136e-05
## R-HSA-390522       3/13  36/10654 9.901474e-06 8.168716e-05 4.169041e-05
## R-HSA-8957275      3/13 108/10654 2.690889e-04 1.775987e-03 9.064048e-04
## R-HSA-381426       3/13 125/10654 4.138114e-04 2.275963e-03 1.161576e-03
## R-HSA-195258       3/13 327/10654 6.517102e-03 3.072348e-02 1.568024e-02
##                                           geneID Count
## R-HSA-445355       59/72/800/4629/4638/7168/7169     7
## R-HSA-397014  59/72/800/1674/4629/4638/7168/7169     8
## R-HSA-5627123                     2316/4629/4638     3
## R-HSA-390522                      1674/7168/7169     3
## R-HSA-8957275                     3488/3490/8404     3
## R-HSA-381426                      3488/3490/8404     3
## R-HSA-195258                      2316/4629/4638     3
## [1] "---------------------------------"
## [1] "=================================="
## 'select()' returned 1:1 mapping between keys and columns
## [1] "cluster_20"
##  [1] "ACP5"     "ACTR3"    "AIF1"     "ALCAM"    "APOC1"    "ARHGDIB" 
##  [7] "ARPC1B"   "B2M"      "C1orf162" "C1QA"     "C1QB"     "CALM3"   
## [13] "CAPG"     "CCDC88A"  "CD163"    "CD52"     "CD68"     "CD74"    
## [19] "CHI3L1"   "CSTB"     "CTSB"     "CTSD"     "CTSS"     "CYBA"    
## [25] "EPB41L2"  "FABP5"    "FBP1"     "FCER1G"   "FTH1"     "FTL"     
## [31] "FYB1"     "GLIPR1"   "GPNMB"    "GRN"      "HCST"     "HLA-B"   
## [37] "HLA-DRA"  "HLA-DRB1" "IGSF6"    "IQGAP2"   "ITGB2"    "LAPTM5"  
## [43] "LCP1"     "LGMN"     "LIPA"     "LSP1"     "LYZ"      "MMP9"    
## [49] "MS4A7"    "MSR1"     "NPC2"     "PLA2G7"   "PLD3"     "PTPRC"   
## [55] "SAMHD1"   "SELENOP"  "SH3BGRL3" "SPP1"     "SRGN"     "STMN1"   
## [61] "TMSB4X"   "TPM3"     "TREM2"    "TUBA1B"   "TYROBP"   "VIM"     
## [1] "---------------------------------"
## [1] "GO Enrichment: "
##                    ID
## GO:0003779 GO:0003779
## GO:0051015 GO:0051015
## GO:0008199 GO:0008199
## GO:0043394 GO:0043394
## GO:0001540 GO:0001540
## GO:0042277 GO:0042277
## GO:0023026 GO:0023026
## GO:0033218 GO:0033218
## GO:0008198 GO:0008198
## GO:0023023 GO:0023023
## GO:0042605 GO:0042605
## GO:0005200 GO:0005200
## GO:0004322 GO:0004322
## GO:0016724 GO:0016724
## GO:0050998 GO:0050998
## GO:0005178 GO:0005178
## GO:0030169 GO:0030169
## GO:0005518 GO:0005518
## GO:0016722 GO:0016722
## GO:0038024 GO:0038024
## GO:0001871 GO:0001871
## GO:0030247 GO:0030247
## GO:0030507 GO:0030507
## GO:0043548 GO:0043548
## GO:0071813 GO:0071813
## GO:0071814 GO:0071814
## GO:0005504 GO:0005504
## GO:0004197 GO:0004197
##                                                                  Description
## GO:0003779                                                     actin binding
## GO:0051015                                            actin filament binding
## GO:0008199                                               ferric iron binding
## GO:0043394                                              proteoglycan binding
## GO:0001540                                              amyloid-beta binding
## GO:0042277                                                   peptide binding
## GO:0023026                              MHC class II protein complex binding
## GO:0033218                                                     amide binding
## GO:0008198                                              ferrous iron binding
## GO:0023023                                       MHC protein complex binding
## GO:0042605                                           peptide antigen binding
## GO:0005200                            structural constituent of cytoskeleton
## GO:0004322                                              ferroxidase activity
## GO:0016724 oxidoreductase activity, oxidizing metal ions, oxygen as acceptor
## GO:0050998                                     nitric-oxide synthase binding
## GO:0005178                                                  integrin binding
## GO:0030169                          low-density lipoprotein particle binding
## GO:0005518                                                  collagen binding
## GO:0016722                     oxidoreductase activity, oxidizing metal ions
## GO:0038024                                           cargo receptor activity
## GO:0001871                                                   pattern binding
## GO:0030247                                            polysaccharide binding
## GO:0030507                                                  spectrin binding
## GO:0043548                             phosphatidylinositol 3-kinase binding
## GO:0071813                                      lipoprotein particle binding
## GO:0071814                                     protein-lipid complex binding
## GO:0005504                                                fatty acid binding
## GO:0004197                              cysteine-type endopeptidase activity
##            GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## GO:0003779     11/61 431/17697 2.200410e-07 4.048755e-05 2.918439e-05
## GO:0051015      7/61 198/17697 5.165028e-06 2.275463e-04 1.640208e-04
## GO:0008199      3/61  11/17697 6.304392e-06 2.275463e-04 1.640208e-04
## GO:0043394      4/61  36/17697 6.928387e-06 2.275463e-04 1.640208e-04
## GO:0001540      5/61  78/17697 7.165458e-06 2.275463e-04 1.640208e-04
## GO:0042277      8/61 295/17697 7.419989e-06 2.275463e-04 1.640208e-04
## GO:0023026      3/61  16/17697 2.113531e-05 5.555567e-04 4.004585e-04
## GO:0033218      8/61 356/17697 2.881579e-05 6.627631e-04 4.777354e-04
## GO:0008198      3/61  24/17697 7.490245e-05 1.531339e-03 1.103826e-03
## GO:0023023      3/61  25/17697 8.490769e-05 1.562302e-03 1.126144e-03
## GO:0042605      3/61  31/17697 1.635136e-04 2.735136e-03 1.971551e-03
## GO:0005200      4/61 102/17697 4.218511e-04 6.468383e-03 4.662565e-03
## GO:0004322      2/61  10/17697 5.166467e-04 6.790214e-03 4.894548e-03
## GO:0016724      2/61  10/17697 5.166467e-04 6.790214e-03 4.894548e-03
## GO:0050998      2/61  14/17697 1.035537e-03 1.270258e-02 9.156324e-03
## GO:0005178      4/61 132/17697 1.110722e-03 1.277330e-02 9.207302e-03
## GO:0030169      2/61  16/17697 1.359497e-03 1.471455e-02 1.060660e-02
## GO:0005518      3/61  67/17697 1.595638e-03 1.631097e-02 1.175734e-02
## GO:0016722      2/61  19/17697 1.924439e-03 1.863667e-02 1.343375e-02
## GO:0038024      3/61  85/17697 3.148539e-03 2.786458e-02 2.008546e-02
## GO:0001871      2/61  25/17697 3.331635e-03 2.786458e-02 2.008546e-02
## GO:0030247      2/61  25/17697 3.331635e-03 2.786458e-02 2.008546e-02
## GO:0030507      2/61  28/17697 4.170088e-03 3.336070e-02 2.404719e-02
## GO:0043548      2/61  30/17697 4.777734e-03 3.662930e-02 2.640327e-02
## GO:0071813      2/61  33/17697 5.760861e-03 4.076917e-02 2.938739e-02
## GO:0071814      2/61  33/17697 5.760861e-03 4.076917e-02 2.938739e-02
## GO:0005504      2/61  34/17697 6.107410e-03 4.162087e-02 3.000131e-02
## GO:0004197      3/61 116/17697 7.493020e-03 4.923985e-02 3.549325e-02
##                                                              geneID Count
## GO:0003779 10096/199/10095/822/55704/2037/10788/3936/4046/7114/7170    11
## GO:0051015                      10096/199/10095/822/10788/3936/7170     7
## GO:0008199                                             54/2495/2512     3
## GO:0043394                                     1508/1520/10457/5788     4
## GO:0001540                                  712/972/3689/4481/54209     5
## GO:0042277                   712/972/3106/3122/3123/3689/4481/54209     8
## GO:0023026                                            972/3122/3123     3
## GO:0033218                   712/972/3106/3122/3123/3689/4481/54209     8
## GO:0008198                                             54/2495/2512     3
## GO:0023023                                            972/3122/3123     3
## GO:0042605                                           3106/3122/3123     3
## GO:0005200                                   10096/10095/10376/7431     4
## GO:0004322                                                2495/2512     2
## GO:0016724                                                2495/2512     2
## GO:0050998                                                  808/972     2
## GO:0005178                                     10457/3689/3936/6696     4
## GO:0030169                                               4481/54209     2
## GO:0005518                                           1508/1520/4318     3
## GO:0016722                                                2495/2512     2
## GO:0038024                                           9332/3689/4481     3
## GO:0001871                                                3122/3123     2
## GO:0030247                                                3122/3123     2
## GO:0030507                                                2037/5788     2
## GO:0043548                                                808/10870     2
## GO:0071813                                               4481/54209     2
## GO:0071814                                               4481/54209     2
## GO:0005504                                                 341/2171     2
## GO:0004197                                           1508/1520/5641     3
## [1] "---------------------------------"
## [1] "Reactome Enrichment: "
##                          ID
## R-HSA-6798695 R-HSA-6798695
## R-HSA-2132295 R-HSA-2132295
## R-HSA-1236977 R-HSA-1236977
## R-HSA-1679131 R-HSA-1679131
## R-HSA-198933   R-HSA-198933
## R-HSA-2173782 R-HSA-2173782
## R-HSA-3000480 R-HSA-3000480
## R-HSA-416700   R-HSA-416700
## R-HSA-202427   R-HSA-202427
## R-HSA-2424491 R-HSA-2424491
## R-HSA-5626467 R-HSA-5626467
## R-HSA-202433   R-HSA-202433
## R-HSA-8964043 R-HSA-8964043
## R-HSA-1474228 R-HSA-1474228
## R-HSA-877300   R-HSA-877300
## R-HSA-2172127 R-HSA-2172127
## R-HSA-1236975 R-HSA-1236975
## R-HSA-166786   R-HSA-166786
## R-HSA-391160   R-HSA-391160
## R-HSA-202403   R-HSA-202403
## R-HSA-913531   R-HSA-913531
## R-HSA-2022090 R-HSA-2022090
## R-HSA-202430   R-HSA-202430
## R-HSA-8964038 R-HSA-8964038
## R-HSA-1442490 R-HSA-1442490
## R-HSA-114608   R-HSA-114608
## R-HSA-373755   R-HSA-373755
##                                                                            Description
## R-HSA-6798695                                                 Neutrophil degranulation
## R-HSA-2132295                                        MHC class II antigen presentation
## R-HSA-1236977                                               Endosomal/Vacuolar pathway
## R-HSA-1679131                              Trafficking and processing of endosomal TLR
## R-HSA-198933  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
## R-HSA-2173782                     Binding and Uptake of Ligands by Scavenger Receptors
## R-HSA-3000480                                          Scavenging by Class A Receptors
## R-HSA-416700                                             Other semaphorin interactions
## R-HSA-202427                                Phosphorylation of CD3 and TCR zeta chains
## R-HSA-2424491                                                          DAP12 signaling
## R-HSA-5626467                                              RHO GTPases activate IQGAPs
## R-HSA-202433                                  Generation of second messenger molecules
## R-HSA-8964043                                             Plasma lipoprotein clearance
## R-HSA-1474228                                  Degradation of the extracellular matrix
## R-HSA-877300                                                Interferon gamma signaling
## R-HSA-2172127                                                       DAP12 interactions
## R-HSA-1236975                                    Antigen processing-Cross presentation
## R-HSA-166786                                          Creation of C4 and C2 activators
## R-HSA-391160                             Signal regulatory protein family interactions
## R-HSA-202403                                                             TCR signaling
## R-HSA-913531                                                      Interferon Signaling
## R-HSA-2022090             Assembly of collagen fibrils and other multimeric structures
## R-HSA-202430                          Translocation of ZAP-70 to Immunological synapse
## R-HSA-8964038                                                            LDL clearance
## R-HSA-1442490                                                     Collagen degradation
## R-HSA-114608                                                   Platelet degranulation 
## R-HSA-373755                                                   Semaphorin interactions
##               GeneRatio   BgRatio       pvalue     p.adjust       qvalue
## R-HSA-6798695     22/57 480/10654 1.208785e-15 3.239544e-13 2.722948e-13
## R-HSA-2132295      8/57 123/10654 2.584295e-07 3.462956e-05 2.910733e-05
## R-HSA-1236977      3/57  11/10654 2.324159e-05 2.076249e-03 1.745158e-03
## R-HSA-1679131      3/57  13/10654 3.998010e-05 2.678667e-03 2.251511e-03
## R-HSA-198933       6/57 132/10654 6.977282e-05 3.163880e-03 2.659349e-03
## R-HSA-2173782      4/57  42/10654 7.083313e-05 3.163880e-03 2.659349e-03
## R-HSA-3000480      3/57  19/10654 1.324027e-04 4.435492e-03 3.728183e-03
## R-HSA-416700       3/57  19/10654 1.324027e-04 4.435492e-03 3.728183e-03
## R-HSA-202427       3/57  22/10654 2.080395e-04 6.194953e-03 5.207069e-03
## R-HSA-2424491      3/57  30/10654 5.320706e-04 1.425949e-02 1.198559e-02
## R-HSA-5626467      3/57  32/10654 6.451082e-04 1.457374e-02 1.224973e-02
## R-HSA-202433       3/57  33/10654 7.069351e-04 1.457374e-02 1.224973e-02
## R-HSA-8964043      3/57  33/10654 7.069351e-04 1.457374e-02 1.224973e-02
## R-HSA-1474228      5/57 140/10654 8.823772e-04 1.689122e-02 1.419765e-02
## R-HSA-877300       4/57  92/10654 1.450212e-03 2.578876e-02 2.167634e-02
## R-HSA-2172127      3/57  43/10654 1.539628e-03 2.578876e-02 2.167634e-02
## R-HSA-1236975      4/57  99/10654 1.900442e-03 2.995991e-02 2.518233e-02
## R-HSA-166786       2/57  14/10654 2.455757e-03 3.656349e-02 3.073286e-02
## R-HSA-391160       2/57  16/10654 3.216205e-03 4.536542e-02 3.813119e-02
## R-HSA-202403       4/57 119/10654 3.704526e-03 4.964065e-02 4.172467e-02
## R-HSA-913531       5/57 199/10654 4.120874e-03 4.978101e-02 4.184264e-02
## R-HSA-2022090      3/57  61/10654 4.195037e-03 4.978101e-02 4.184264e-02
## R-HSA-202430       2/57  19/10654 4.536184e-03 4.978101e-02 4.184264e-02
## R-HSA-8964038      2/57  19/10654 4.536184e-03 4.978101e-02 4.184264e-02
## R-HSA-1442490      3/57  64/10654 4.801827e-03 4.978101e-02 4.184264e-02
## R-HSA-114608       4/57 129/10654 4.937619e-03 4.978101e-02 4.184264e-02
## R-HSA-373755       3/57  65/10654 5.015251e-03 4.978101e-02 4.184264e-02
##                                                                                                                       geneID
## R-HSA-6798695 567/968/1116/1476/1508/1509/1520/1535/2171/2207/2495/2512/11010/2896/3106/10788/3689/4069/4318/10577/5788/7305
## R-HSA-2132295                                                                        972/1508/1509/1520/3122/3123/5641/10376
## R-HSA-1236977                                                                                                  567/1520/3106
## R-HSA-1679131                                                                                                 1508/1520/5641
## R-HSA-198933                                                                                  567/10870/3106/3689/54209/7305
## R-HSA-2173782                                                                                            9332/2495/2512/4481
## R-HSA-3000480                                                                                                 2495/2512/4481
## R-HSA-416700                                                                                                 5788/54209/7305
## R-HSA-202427                                                                                                  3122/3123/5788
## R-HSA-2424491                                                                                                 567/54209/7305
## R-HSA-5626467                                                                                                808/10788/10376
## R-HSA-202433                                                                                                  2533/3122/3123
## R-HSA-8964043                                                                                                 341/3988/10577
## R-HSA-1474228                                                                                       1508/1509/1520/4318/6696
## R-HSA-877300                                                                                              567/3106/3122/3123
## R-HSA-2172127                                                                                                 567/54209/7305
## R-HSA-1236975                                                                                             567/1520/1535/3106
## R-HSA-166786                                                                                                         712/713
## R-HSA-391160                                                                                                       2533/7305
## R-HSA-202403                                                                                             2533/3122/3123/5788
## R-HSA-913531                                                                                        567/3106/3122/3123/25939
## R-HSA-2022090                                                                                                 1508/1520/4318
## R-HSA-202430                                                                                                       3122/3123
## R-HSA-8964038                                                                                                     3988/10577
## R-HSA-1442490                                                                                                 1508/1509/4318
## R-HSA-114608                                                                                              808/6414/5552/7114
## R-HSA-373755                                                                                                 5788/54209/7305
##               Count
## R-HSA-6798695    22
## R-HSA-2132295     8
## R-HSA-1236977     3
## R-HSA-1679131     3
## R-HSA-198933      6
## R-HSA-2173782     4
## R-HSA-3000480     3
## R-HSA-416700      3
## R-HSA-202427      3
## R-HSA-2424491     3
## R-HSA-5626467     3
## R-HSA-202433      3
## R-HSA-8964043     3
## R-HSA-1474228     5
## R-HSA-877300      4
## R-HSA-2172127     3
## R-HSA-1236975     4
## R-HSA-166786      2
## R-HSA-391160      2
## R-HSA-202403      4
## R-HSA-913531      5
## R-HSA-2022090     3
## R-HSA-202430      2
## R-HSA-8964038     2
## R-HSA-1442490     3
## R-HSA-114608      4
## R-HSA-373755      3
## [1] "---------------------------------"
## [1] "=================================="
fname <- paste0(ANALYSIS_ID, ".markers_pathwayenrichment.xlsx")

sheets <- list()
for (c_name in names(pw_results_go)) {
  pw_res <- pw_results_go[[c_name]]@result
  sheets[paste0("GO_",c_name)] <- list(pw_res)
}

for (c_name in names(pw_results_ra)) {
  pw_res <- pw_results_ra[[c_name]]@result
  sheets[paste0("RA_",c_name)] <- list(pw_res)
}

write_xlsx(
  x = sheets,
  path = file.path(DIR_RES, "tables", fname),
  col_names = TRUE,
  format_headers = TRUE
)





Other

Correlation of marker genes with LEP expression

markers_C3 <- FindMarkers(se, ident.1 = "3", only.pos = T, logfc.threshold = 0.15)
markers_C4 <- FindMarkers(se, ident.1 = "4", only.pos = T, logfc.threshold = 0.15)
genes_corr <- c(rownames(markers_C3), rownames(markers_C4))

exp_mat <- as.matrix(se@assays$SCT@data[genes_corr, ])
exp_goi <- as.numeric(exp_mat["LEP",])

gene_corr <- apply(exp_mat, 1, function(x){cor(exp_goi, x)})

gene_df_out <- data.frame(gene = genes_corr,
                          corr = gene_corr,
                          cluster = c(rep("C3", length(rownames(markers_C3))), rep("C4", length(rownames(markers_C4))) )
                          )
gene_df_out <- gene_df_out[!rownames(gene_df_out) %in% "LEP", ]

p1 <- ggplot(gene_df_out, aes(x=cluster, y=corr)) +
  geom_boxplot() +
  theme_linedraw()

p2 <- ggplot(gene_df_out, aes(x=reorder(gene, corr), y=corr, fill=cluster)) +
  geom_col() +
  labs(x="") +
  coord_flip() +
  theme_linedraw()

p <- (p1+p2) + plot_annotation(title="Gene correlations with LEP");p

pdf(file = file.path(DIR_FIG, "LEP_gene_corr_C3-C4.pdf"), width = 10, height = 8, useDingbats = F);p;dev.off()
## quartz_off_screen 
##                 2
write.csv(gene_df_out, file.path(DIR_FIG, "LEP_gene_corr_C3-C4.csv"), row.names = F)

Cell signature expression

Adapted cell signatures for ATM from Acosta et al. (2017) (DOI 10.1186/s13287-017-0701-4).

cellsign_list <- list(ATM_M1 = c("HLA-DRA", "HLA-DPA1", "HLA-DPB1", "HLA-DRB5", "FCER1A", "CD1C", "IL1R2", "HLA-DQA2", "HLA-DRB3"),
                      ATM_M2 = c("RNASE1", "SEPP1", "JUND", "DNAJB1", "LYVE1", "MAF", "MAFB", "F13A1", "RHOB", "TRA2B"),
                      ATM_Int = c("FTL", "FTH1", "CTSB", "CCL3", "PLIN2", "FABP5", "PSAP", "CCL4", "CTSD", "IL1RN"))

cell_spot_sign <- list()
for ( cell in names(cellsign_list)){
  # print(cell)
  cell_signature_genes <- cellsign_list[[cell]]
  cell_signature_genes_intersect <- intersect(cell_signature_genes, rownames(se))
  print(c(cell, paste(cell_signature_genes_intersect)))
  cell_spot_sign[[cell]] <- colSums(GetAssayData(se, slot = "data", assay = "SCT")[cell_signature_genes_intersect, ])
  print(summary(cell_spot_sign[[cell]]))
  se <- AddMetaData(se, cell_spot_sign[[cell]], col.name = cell)
}
## [1] "ATM_M1"   "HLA-DRA"  "HLA-DPA1" "HLA-DPB1" "HLA-DRB5" "FCER1A"   "HLA-DQA2"
##    Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
##  0.0000  0.0000  0.0000  0.3344  0.6931  7.2724 
##  [1] "ATM_M2" "RNASE1" "JUND"   "DNAJB1" "LYVE1"  "MAF"    "MAFB"   "F13A1" 
##  [9] "RHOB"   "TRA2B" 
##    Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
##  0.0000  0.0000  0.6931  0.9936  1.3863  7.3369 
## [1] "ATM_Int" "FTL"     "FTH1"    "CTSB"    "PLIN2"   "FABP5"   "PSAP"   
## [8] "CTSD"   
##    Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
##   0.000   3.989   4.970   5.052   6.061  20.308
cut_M1 <- median(se@meta.data[se@meta.data$ATM_M1>0, "ATM_M1"])
# print(cut_M1)

se@meta.data$ATM_M1_cat <- "low"
se@meta.data[se@meta.data$ATM_M1 > cut_M1, "ATM_M1_cat"] <- "high"

df_M1_prop <- se@meta.data
df_M1_prop <- df_M1_prop %>%
  group_by(condition, subject_alias, ATM_M1_cat) %>%
  dplyr::count()

df_M1_prop$pct <- 0
for(s in unique(df_M1_prop$subject_alias)) {
  sum_spots <- sum(df_M1_prop[df_M1_prop$subject_alias %in% s, "n"])
  df_M1_prop[df_M1_prop$subject_alias %in% s, "pct"] <- (round(df_M1_prop[df_M1_prop$subject_alias %in% s, "n"] / sum_spots, digits = 3))*100
}

df_M1_prop$cut <- cut_M1
df_M1_prop
## # A tibble: 20 x 6
## # Groups:   condition, subject_alias, ATM_M1_cat [20]
##    condition  subject_alias ATM_M1_cat     n   pct   cut
##    <chr>      <chr>         <chr>      <int> <dbl> <dbl>
##  1 lean       Le.1          high          88   4.2 0.693
##  2 lean       Le.1          low         1993  95.8 0.693
##  3 lean       Le.2          high         326  15   0.693
##  4 lean       Le.2          low         1854  85   0.693
##  5 lean       Le.3          high         445  11.3 0.693
##  6 lean       Le.3          low         3504  88.7 0.693
##  7 obese      Ob.1          high         287   8.2 0.693
##  8 obese      Ob.1          low         3210  91.8 0.693
##  9 obese      Ob.2          high         207  12.8 0.693
## 10 obese      Ob.2          low         1406  87.2 0.693
## 11 obese      Ob.3          high         300   6.6 0.693
## 12 obese      Ob.3          low         4220  93.4 0.693
## 13 obese      Ob.4          high         468  24   0.693
## 14 obese      Ob.4          low         1482  76   0.693
## 15 obese      Ob.5          high         593  26.8 0.693
## 16 obese      Ob.5          low         1622  73.2 0.693
## 17 overweight Ov.1          high         409  21.9 0.693
## 18 overweight Ov.1          low         1458  78.1 0.693
## 19 overweight Ov.2          high         647  15.9 0.693
## 20 overweight Ov.2          low         3418  84.1 0.693




Plots

QC

feat_plot <- c("nFeature_RNA", "nCount_RNA", "percent.mt", "percent.MTRNR", "percent.HB.genes", "percent.MALAT1", "percent.RP")
VlnPlot(se, group.by = "sample_id", 
        features = feat_plot, 
        ncol = length(feat_plot), 
        pt.size = 0)

p <- VlnPlot(se, 
            group.by = "subject_alias", 
            features = c("nFeature_RNA", "nCount_RNA"), 
            ncol = 2, 
            cols = c(rep(colors_multi[1], 3), rep(colors_multi[2], 5), rep(colors_multi[3], 2)),
            pt.size = 0) & 
  scale_y_log10() &
  theme(axis.title.x = element_blank()) & 
  geom_boxplot(width=0.2, outlier.size = .5);p

fname <- paste0(ANALYSIS_ID, ".qc_stats_violin")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 6, height = 4);p;dev.off()
## quartz_off_screen 
##                 2
d_plot <- data.frame(se[[]])
d_plot1 <- d_plot[, c("subject_alias", "nCount_RNA")]
colnames(d_plot1) <- c("subject_alias", "qc_value")
d_plot1$qc_stat <- "UMIs"

d_plot2 <- d_plot[, c("subject_alias", "nFeature_RNA")]
colnames(d_plot2) <- c("subject_alias", "qc_value")
d_plot2$qc_stat <- "Genes"

d_plot3 <- rbind(d_plot1, d_plot2)

p <- ggplot(d_plot3, aes(x=qc_stat, y=qc_value)) +
  geom_violin(fill="grey80", color=NA) +
  geom_boxplot(width=0.2, outlier.size = 0.2) +
  scale_y_log10() +
  annotation_logticks(sides = "l") +
  labs(title="", x="", y="count per spot") +
  theme_classic() +
  theme(plot.title = element_text(hjust=0.5, face = "bold"), legend.position = "none", legend.title = element_blank());p

fname <- paste0(ANALYSIS_ID, ".qc_stats_violin2")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 3, height = 3);p;dev.off()
## quartz_off_screen 
##                 2
color_scale <- c("white", "orange", "red")
p1 <- ST.FeaturePlot(se, features = c("percent.mt"), dark.theme = F, cols = color_scale, max.cutoff = 40)
p2 <- ST.FeaturePlot(se, features = c("percent.HB.genes"), dark.theme = F, cols = color_scale, max.cutoff = 20)
p3 <- ST.FeaturePlot(se, features = c("percent.MTRNR"), dark.theme = F, cols = color_scale)
p4 <- ST.FeaturePlot(se, features = c("percent.MALAT1"), dark.theme = F, cols = color_scale)
p5 <- ST.FeaturePlot(se, features = c("percent.RP"), dark.theme = F, cols = color_scale)

p <- (p1+p2+p3)/(p4+p5+patchwork::plot_spacer());p

fname <- paste0(ANALYSIS_ID, ".qc_stats_spatial")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 32, height = 18);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 32*2.8, height = 18*2.8, res = 600); p; dev.off()
## quartz_off_screen 
##                 2



Dimensionality reduction

ICA

fname <- paste0(ANALYSIS_ID, ".dimred_ica_hm")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 14, height = 20)
p1 <- DimHeatmap(se, dims = 1:18, cells = 500, nfeatures = 16, balanced = TRUE, reduction = "ica", ncol = 3);p1
## NULL
p2 <- DimHeatmap(se, dims = 19:36, cells = 500, nfeatures = 16, balanced = TRUE, reduction = "ica", ncol = 3);p2
## NULL
p3 <- DimHeatmap(se, dims = 37:50, cells = 500, nfeatures = 16, balanced = TRUE, reduction = "ica", ncol = 3);p3
## NULL
dev.off()
## quartz_off_screen 
##                 2

Harmony

fname <- paste0(ANALYSIS_ID, ".dimred_harmony_hm")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 14, height = 20)
p1 <- DimHeatmap(se, dims = 1:18, cells = 500, nfeatures = 16, balanced = TRUE, reduction = "harmony", ncol = 3);p1
## NULL
p2 <- DimHeatmap(se, dims = 19:36, cells = 500, nfeatures = 16, balanced = TRUE, reduction = "harmony", ncol = 3);p2
## NULL
p3 <- DimHeatmap(se, dims = 37:50, cells = 500, nfeatures = 16, balanced = TRUE, reduction = "harmony", ncol = 3);p3
## NULL
dev.off()
## quartz_off_screen 
##                 2

UMAP

pt_size <- 0.25
p1 <- DimPlot(object = se, dims = c(1,2), reduction = "umap", group.by = "subject_alias", pt.size = pt_size, cols = colors_multi) + NoAxes() #+ DarkTheme()
p2 <- DimPlot(object = se, dims = c(1,2), reduction = "umap", group.by = "condition", pt.size = pt_size, cols = colors_multi) + NoAxes() #+ DarkTheme()
p3 <- FeaturePlot(object = se, dims = c(1,2), reduction = "umap", features = "nCount_RNA", pt.size = pt_size, cols = c("grey90", "red"), max.cutoff = 5000) + NoAxes()
p4 <- FeaturePlot(object = se, dims = c(1,2), reduction = "umap", features = "nFeature_RNA", pt.size = pt_size, cols = c("grey90", "red")) + NoAxes()
p <- (p1-p2)/(p3-p4);p

fname <- paste0(ANALYSIS_ID, ".dimred_umap_qc_stats")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 10, height = 8.5);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 10*2.5, height = 8.5*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2
p <- DimPlot(object = se, 
             reduction = "umap", dims = c(1,2), 
             group.by = "subject_alias",
             cols = colors_multi) + 
  NoAxes();
fname <- paste0(ANALYSIS_ID, ".dimred_umap_subject")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 6, height = 5);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 6*2.5, height = 5*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2
pt_size <- 0.25
plot_gene_umap <- function(se, gene, pt_size = 0.1){
  p <- FeaturePlot(object = se, features = gene, 
                   reduction = "umap", pt.size = pt_size, 
                   slot = "scale.data", min.cutoff = 0,
                   cols = c("grey90", "red")) + NoAxes()
  return(p)
}

plot_grid(plot_gene_umap(se, "SAA1"),
          plot_gene_umap(se, "PLIN4"),
          plot_gene_umap(se, "ADIPOQ"),
          plot_gene_umap(se, "LEP"),
          plot_gene_umap(se, "MRC1"),
          plot_gene_umap(se, "CD68"),
          plot_gene_umap(se, "IGKC"),
          plot_gene_umap(se, "TPSB2"),
          plot_gene_umap(se, "NKG7"),
          ncol = 3)

pt_size <- 0.5
p1 <- DimPlot(object = se, dims = c(1,2), reduction = "umapICA", group.by = "subject_alias", pt.size = pt_size, cols = colors_multi) + NoAxes()
p2 <- DimPlot(object = se, dims = c(1,2), reduction = "umapICA", group.by = "condition", pt.size = pt_size, cols = colors_multi) + NoAxes()

p <- p1-p2;p

fname <- paste0(ANALYSIS_ID, ".dimred_umap_ica")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 10, height = 5);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 12*2.5, height = 5*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2



Clustering

Clustree

p <- clustree(se, prefix = "SCT_snn_res.", node_colour = "grey70");p

fname <- paste0(ANALYSIS_ID, ".clustering_clustree")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 12, height = 10);p;dev.off()
## quartz_off_screen 
##                 2

Annotations

p <- ggplot(c_anno, aes(seurat_clusters, 0, color = cluster_anno)) +
  geom_point(size=3) +
  scale_colour_manual(values = c_anno$cluster_color) +
  scale_x_continuous(n.breaks = 20) +
  scale_y_continuous(n.breaks = 2) +
  theme_classic() +
  theme(legend.position = 'top', 
        axis.title.y = element_blank(), axis.ticks.y = element_blank(), axis.text.y = element_blank(), axis.line.y = element_blank());p

fname <- paste0(ANALYSIS_ID, ".clustering_annotationlegend")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 10, height = 2);p;dev.off()
## quartz_off_screen 
##                 2
cluster_prop <- merge(cluster_prop, c_anno, by="seurat_clusters")
se_markers <- merge(x = se_markers, y = c_anno, by.x="cluster", by.y="seurat_clusters")

UMAP

dims_test <- paste0("SCT_snn_res.", c(0.8, 0.9, 1, 1.2, 1.6, 2))
DimPlot(object = se, dims = c(1,2), reduction = "umap", group.by = dims_test, 
        pt.size = 0.5,
        label = T, label.size = 5, ncol = 3) & NoLegend()

p <- DimPlot(object = se, 
             reduction = "umap", dims = c(1,2), 
             group.by = "seurat_clusters",
             cols = c_anno[order(as.numeric(c_anno$seurat_clusters)),]$cluster_color,
             label = T, 
             label.size = 8, 
             repel = F) + 
  NoAxes(); p

p2 <- DimPlot(object = se, 
             reduction = "umap", dims = c(1,2), 
             group.by = "seurat_clusters",
             cols = c_anno[order(as.numeric(c_anno$seurat_clusters)),]$cluster_color,
             label = F) + 
  NoAxes() + NoLegend();

fname <- paste0(ANALYSIS_ID, ".clustering_umap")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 6, height = 5);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 6*2.5, height = 5*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2
# tiff(filename = file.path(DIR_FIG, paste0(fname, "2.tiff")), units = "pt", width = 190, height = 192, res = 600); p; dev.off()  # TODO: !



fname <- paste0(ANALYSIS_ID, ".clustering_umap_b")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 4.8, height = 5);p2;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 4.8*2.5, height = 5*2.5, res = 600); p2; dev.off()
## quartz_off_screen 
##                 2

Spot proportions

d_plot <- cluster_prop

p1 <- ggplot(d_plot, aes(x = as.factor(subject), y = n, fill = as.factor(seurat_clusters))) + 
  geom_bar(stat = 'identity', colour=NA, position = "stack") +
  scale_fill_manual(values = c_anno[order(c_anno$seurat_clusters), "cluster_color"]) +
  labs(x="", y="# Spots", fill="") +
  theme_minimal() +
  theme(axis.text.x = element_text(angle = 90, vjust = 0.5, hjust = 1),
        legend.position = "top", legend.text = element_text(size=6))

p2 <- ggplot(d_plot, aes(x = as.factor(seurat_clusters), y = n, fill = subject)) + 
  geom_bar(stat = 'identity', colour="white", position = "stack") +
  scale_fill_manual(values = colors_multi) +
  scale_y_log10() +
  labs(x="", y="# Spots (log10)", fill="") +
  theme_minimal() +
  theme(axis.text.x = element_text(angle = 90, vjust = 0.5, hjust = 1),
        legend.position = "top")

p3 <- ggplot(d_plot, aes(x = as.factor(seurat_clusters), y = n, fill = subject)) +
  geom_bar(stat = 'identity', colour="white", position = "fill") +
  scale_fill_manual(values = colors_multi) +
  labs(x="", y="Spot proportions", fill="") +
  theme_minimal() +
  theme(axis.text.x = element_text(angle = 90, vjust = 0.5, hjust = 1),
        legend.position = "top")

p <- plot_grid(p1, p2, p3, nrow = 1, rel_heights = c(0.55, 0.45));p

fname <- paste0(ANALYSIS_ID, ".clustering_countspots")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 10, height = 6);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 10*2.5, height = 6*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2
d_plot <- subset(cluster_prop, cluster_group %in% "Adipocyte")
p <- ggplot(d_plot, aes(x=as.numeric(bmi), y=cluster_pct_subject)) +
  geom_line(color = "grey80") +
  geom_point(size=2, aes(color=bmi)) +
  scale_color_gradient(low = colors_main[1], high = colors_main[2]) +
  scale_y_continuous(limits = c(0,15)) +
  facet_grid(~cluster_anno) +
  labs(y="Cluster proportion (%)", x="BMI") +
  theme_classic() +
  theme(legend.position = "none", strip.background = element_blank(), strip.text = element_text(face = "bold")); p

fname <- paste0(ANALYSIS_ID, ".clustering_countspots_corr-bmi")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 6, height = 2.5);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 6*2.5, height = 2.5*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2



Cluster marker genes

Cluster DEA

top_dotp <- se_markers %>% group_by(cluster) %>% dplyr::top_n(n = 2, wt = avg_logFC) %>% dplyr::arrange(as.numeric(cluster))
top_dotp_add <- se_markers %>% group_by(cluster) %>% dplyr::filter(gene %in% c("ADIPOQ", "SORBS1"))
top_dotp <- rbind(top_dotp, top_dotp_add) %>% dplyr::arrange((cluster_anno))


p1 <- DotPlot(se, features = rev(unique(top_dotp$gene)), 
             col.min = -2, col.max = 2,
             group.by = "cluster_anno",
             scale = T,
             cols = c("grey90", "red")) + rotate() +
  scale_colour_gradient2(low = "#441153", mid = "grey90", high = "#3CB67B") +
  theme(axis.title.x = element_blank(),
        axis.text.x = element_text(angle = 90, hjust = 1, vjust = 0.5),
        axis.title.y = element_blank()); p1

fname <- paste0(ANALYSIS_ID, ".markers_clusterdea_dotplot_a")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 7, height = 11); p1;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 7*2.5, height = 11*2.5, res = 600); p1; dev.off()
## quartz_off_screen 
##                 2
ggsave(filename = file.path(DIR_FIG, paste0(fname, ".eps")), plot = p1, width = 7, height = 11)
p2 <- DotPlot(se, features = rev(unique(top_dotp$gene)),
             col.min = -2, col.max = 2,
             group.by = "cluster_anno",
             scale = T,
             cols = c("grey90", "red") ) +
  scale_colour_gradient2(low = "#441153", mid = "grey90", high = "#3CB67B") +
  theme(axis.title.x = element_blank(),
    axis.text.x = element_text(angle = 90, hjust = 1, vjust = 0.5),
    axis.title.y = element_blank()); p2

fname <- paste0(ANALYSIS_ID, ".markers_clusterdea_dotplot_b")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 12, height = 5.4); p2;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 30, height = 8*1.8, res = 600); p2; dev.off()
## quartz_off_screen 
##                 2
ggsave(filename = file.path(DIR_FIG, paste0(fname, ".eps")), plot = p2, width = 12, height = 5.4)

# fname <- paste0(ANALYSIS_ID, ".markers_clusterdea_dotplot_test7")
# pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 12, height = 5.4); p2;dev.off()
# ggsave(filename = file.path(DIR_FIG, paste0(fname, ".eps")), plot = p2, width = 12, height = 5.4)
top_hm <- se_markers %>% group_by(cluster) %>% dplyr::top_n(n = 5, wt = avg_logFC) %>% dplyr::arrange(as.numeric(cluster))
p <- DoHeatmap(se,
               features = top_hm$gene, 
               group.colors = c_anno[order(c_anno$seurat_clusters), "cluster_color"],
               angle = 0, hjust = 0, size = 5,
               disp.min = -2.5, disp.max = 2.5) +
  scale_fill_gradientn(colours = rev(RColorBrewer::brewer.pal(5, "RdBu")));

fname <- paste0(ANALYSIS_ID, ".markers_clusterdea_heatmap")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 22, height = 16);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 22*2.5, height = 16*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2


Pathway enrichment

top_pw_dot <- 3
top_pw_df_list <- list()
top_pw_list <- c()
for(c in 1:length(names(markers_seu_clusters))){
  clus <- paste0("cluster_", (c+1))
  if(!is.null(pw_results_go[[clus]])){
    top_pws <- pw_results_go[[clus]][1:top_pw_dot,]$Description
    top_pw_list <- c(top_pw_list, top_pws)
    }
}
top_pw_list <- top_pw_list[!is.na(top_pw_list)]
top_pw_list <- unique(top_pw_list)
for(c in 1:length(names(markers_seu_clusters))){
  clus <- paste0("cluster_", (c+1))
  if(!is.null(pw_results_go[[clus]])){
    pw_res <- pw_results_go[[clus]]@result
    pw_res <- pw_res[pw_res$Description %in% top_pw_list, ]
    df <- data.frame(Cluster = (c+1),
                     Pathway = pw_res$Description,
                     # Pathway_DB = "GO",
                     GeneRatio = pw_res$GeneRatio,
                     p.adjust = pw_res$p.adjust)
    top_pw_df_list[[clus]] <- df
    }
  }
pw_df <- do.call("rbind", top_pw_df_list)
pw_df$cluster <- (as.numeric(pw_df$Cluster))
df_gr <- data.frame(do.call(rbind, strsplit(as.character(pw_df$GeneRatio), split = "/")), stringsAsFactors = F)
generatio <- round(as.numeric(df_gr$X1) / as.numeric(df_gr$X2), 2)
pw_df2 <- merge(pw_df, c_anno, by.x = "Cluster", by.y="seurat_clusters")
pw_df2$GeneRatio <- generatio
pw_df2 <- pw_df2[order(pw_df2$cluster_anno), ]
pw_df2 <- pw_df2 %>% group_by(cluster_anno) %>% dplyr::top_n(n = top_pw_dot, wt = GeneRatio) %>% dplyr::arrange(as.character(Pathway))
p1 <- ggplot(pw_df2, aes(x=cluster_anno, y=Pathway, size=GeneRatio, color=-log10(p.adjust))) +
  geom_point() +
  scale_colour_gradient(low = "#c4e7d1", high = "#3CB67B", breaks=seq(0,20,4)) +
  labs(x="", y="") +
  theme_classic() +
  theme(axis.title.x = element_blank(),
      axis.text.x = element_text(angle = 90, hjust = 1, vjust = 0.5),
      axis.title.y = element_blank(),
      axis.text.y = element_text(size=6), 
      panel.grid = element_line(), 
      panel.grid.major = element_line(colour = "grey95")); p1

fname <- paste0(ANALYSIS_ID, ".markers_pea_GO_a")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 8, height = 7);p1;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 8*2.5, height = 7*2.5, res = 600); p1; dev.off()
## quartz_off_screen 
##                 2
ggsave(filename = file.path(DIR_FIG, paste0(fname, ".eps")), plot = p1, width = 8, height = 7)
p2 <- ggplot(pw_df2, aes(y=cluster_anno, x=Pathway, size=GeneRatio, color=-log10(p.adjust))) +
  geom_point() +
  scale_colour_gradient(low = "#c4e7d1", high = "#3CB67B", breaks=seq(0,20,4)) +
  labs(x="", y="") +
  theme_classic() +
  theme(axis.title.x = element_blank(),
      axis.text.y = element_text(angle = 0, hjust = 1, vjust = 0.5),
      axis.title.y = element_blank(),
      axis.text.x = element_text(angle = 45, hjust = 1, vjust = 1, size=6), 
      panel.grid = element_line(), 
      panel.grid.major = element_line(colour = "grey95")); p2

fname <- paste0(ANALYSIS_ID, ".markers_pea_GO_b")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 8, height = 6);p2;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 8*2.5, height = 6*2.5, res = 600); p2; dev.off()
## quartz_off_screen 
##                 2
ggsave(filename = file.path(DIR_FIG, paste0(fname, ".eps")), plot = p2, width = 8, height = 6)
top_pw_dot <- 3
top_pw_df_list <- list()
top_pw_list <- c()
for(c in 1:length(names(markers_seu_clusters))){
  clus <- paste0("cluster_", (c+1))
  if(!is.null(pw_results_ra[[clus]])){
    top_pws <- pw_results_ra[[clus]][1:top_pw_dot,]$Description
    top_pw_list <- c(top_pw_list, top_pws)
    }
}
top_pw_list <- top_pw_list[!is.na(top_pw_list)]
top_pw_list <- unique(top_pw_list)
for(c in 1:length(names(markers_seu_clusters))){
  clus <- paste0("cluster_", (c+1))
  if(!is.null(pw_results_ra[[clus]])){
    pw_res <- pw_results_ra[[clus]]@result
    pw_res <- pw_res[pw_res$Description %in% top_pw_list, ]
    df <- data.frame(Cluster = (c+1),
                     Pathway = pw_res$Description,
                     GeneRatio = pw_res$GeneRatio,
                     p.adjust = pw_res$p.adjust)
    top_pw_df_list[[clus]] <- df
    }
  }

pw_df_ra <- do.call("rbind", top_pw_df_list)
pw_df_ra$cluster <- (as.numeric(pw_df_ra$Cluster))
df_gr <- data.frame(do.call(rbind, strsplit(as.character(pw_df_ra$GeneRatio), split = "/")), stringsAsFactors = F)
generatio <- round(as.numeric(df_gr$X1) / as.numeric(df_gr$X2), 2)
pw_df_ra2 <- merge(pw_df_ra, c_anno, by.x = "Cluster", by.y="seurat_clusters")
pw_df_ra2$GeneRatio <- generatio
pw_df_ra2 <- pw_df_ra2[order(pw_df_ra2$cluster_anno), ]
pw_df_ra2 <- pw_df_ra2 %>% group_by(cluster_anno) %>% dplyr::top_n(n = top_pw_dot, wt = GeneRatio)
p1 <- ggplot(pw_df_ra2, aes(x=cluster_anno, y=Pathway, size=GeneRatio, color=-log10(p.adjust))) +
  geom_point() +
  scale_colour_gradient(low = "#c4e7d1", high = "#3CB67B", breaks=seq(0,20,4)) +
  labs(x="", y="") +
  theme_classic() +
  theme(axis.title.x = element_blank(),
      axis.text.x = element_text(angle = 90, hjust = 1, vjust = 0.5),
      axis.title.y = element_blank(),
      axis.text.y = element_text(size=6), 
      panel.grid = element_line(), 
      panel.grid.major = element_line(colour = "grey95")); p1

fname <- paste0(ANALYSIS_ID, ".markers_pea_RA_a")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 8, height = 7);p1;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 8*2.5, height = 7*2.5, res = 600); p1; dev.off()
## quartz_off_screen 
##                 2
ggsave(filename = file.path(DIR_FIG, paste0(fname, ".eps")), plot = p1, width = 8, height = 7)
p2 <- ggplot(pw_df_ra2, aes(y=cluster_anno, x=Pathway, size=GeneRatio, color=-log10(p.adjust))) +
  geom_point() +
  scale_colour_gradient(low = "#c4e7d1", high = "#3CB67B", breaks=seq(0,20,4)) +
  labs(x="", y="") +
  theme_classic() +
  theme(axis.title.x = element_blank(),
      axis.text.y = element_text(angle = 0, hjust = 1, vjust = 0.5),
      axis.title.y = element_blank(),
      axis.text.x = element_text(angle = 45, hjust = 1, vjust = 1, size=6), 
      panel.grid = element_line(), 
      panel.grid.major = element_line(colour = "grey95")); p2

fname <- paste0(ANALYSIS_ID, ".markers_pea_RA_b")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 8, height = 6);p2;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 8*2.5, height = 6*2.5, res = 600); p2; dev.off()
## quartz_off_screen 
##                 2
ggsave(filename = file.path(DIR_FIG, paste0(fname, ".eps")), plot = p2, width = 8, height = 6)



Other

LEP and ADIPOQ expression in subjects

All spots

d_plot <- se[[]]
d_plot$LEP <- GetAssayData(se, slot = "scale.data", assay = "SCT")["LEP", ]
d_plot$ADIPOQ <- GetAssayData(se, slot = "scale.data", assay = "SCT")["ADIPOQ", ]

p1 <- ggplot(d_plot, aes(x=factor(bmi), y=LEP, fill = gender)) +
  geom_hline(yintercept = 0, color = "grey70") +
  geom_violin(color=NA) +
  geom_boxplot(width=0.1, outlier.size = 0.2) +
  scale_fill_manual(values = colors_multi[c(2,6)]) +
  labs(title="LEP", x="BMI", y="Norm. scaled expression") +
  theme_classic() +
  theme(plot.title = element_text(hjust=0.5, face = "bold"), legend.position = "bottom", legend.title = element_blank())

p2 <- ggplot(d_plot, aes(x=factor(bmi), y=ADIPOQ, fill = gender)) +
  geom_hline(yintercept = 0, color = "grey70") +
  geom_violin(color=NA) +
  geom_boxplot(width=0.1, outlier.size = 0.2) +
  scale_fill_manual(values = colors_multi[c(2,6)]) +
  labs(title="ADIPOQ", x="BMI", y="Norm. scaled expression") +
  theme_classic() +
  theme(plot.title = element_text(hjust=0.5, face = "bold"), legend.position = "bottom", legend.title = element_blank())

p <- p1-p2;p

fname <- paste0(ANALYSIS_ID, ".other_geneexpr_LEP_ADIPOQ")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 8, height = 3.5);p;dev.off()
## quartz_off_screen 
##                 2
tiff(file = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 8*2.5, height = 3.5*2.5, res=600);p;dev.off()
## quartz_off_screen 
##                 2

Adipocyte spots

d_plot <- subset(se[[]], cluster_group == "Adipocyte")
d_plot$LEP <- GetAssayData(se[,rownames(d_plot)], slot = "scale.data", assay = "SCT")["LEP", ]
d_plot$ADIPOQ <- GetAssayData(se[,rownames(d_plot)], slot = "scale.data", assay = "SCT")["ADIPOQ", ]

p1 <- ggplot(d_plot, aes(x=factor(bmi), y=LEP, fill = gender)) +
  geom_hline(yintercept = 0, color = "grey70") +
  geom_violin(color=NA) +
  geom_boxplot(width=0.2, outlier.size = 0.2) +
  scale_fill_manual(values = colors_multi[c(2,6)]) +
  facet_wrap(~cluster_anno) +
  labs(title="LEP", x="BMI", y="Norm. scaled expression") +
  theme_classic() +
  theme(plot.title = element_text(hjust=0.5, face = "bold"), legend.position = "bottom", legend.title = element_blank(),
        axis.text.x = element_text(angle = 45, hjust = 1, vjust = 1),
        strip.background = element_blank(), strip.text = element_text(face = "bold"))

p2 <- ggplot(d_plot, aes(x=factor(bmi), y=ADIPOQ, fill = gender)) +
  geom_hline(yintercept = 0, color = "grey70") +
  geom_violin(color=NA) +
  geom_boxplot(width=0.2, outlier.size = 0.2) +
  scale_fill_manual(values = colors_multi[c(2,6)]) +
  facet_wrap(~cluster_anno) +
  labs(title="ADIPOQ", x="BMI", y="Norm. scaled expression") +
  theme_classic() +
  theme(plot.title = element_text(hjust=0.5, face = "bold"), legend.position = "bottom", legend.title = element_blank(),
        axis.text.x = element_text(angle = 45, hjust = 1, vjust = 1),
        strip.background = element_blank(), strip.text = element_text(face = "bold"))

p <- p1-p2;p

fname <- paste0(ANALYSIS_ID, ".other_geneexpr_LEP_ADIPOQ_adipocytes")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 12, height = 3.5);p;dev.off()
## quartz_off_screen 
##                 2
tiff(file = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 12*2.5, height = 3.5*2.5, res=600);p;dev.off()
## quartz_off_screen 
##                 2

M1 signauture

p <- ggplot(subset(df_M1_prop, ATM_M1_cat == "high"), aes(x = "", y = pct, fill = ATM_M1_cat)) +
  geom_bar(stat = 'identity', position = "stack", width=0.7) + 
  scale_fill_manual(values = c("orangered", "grey70")) +
  facet_wrap(~subject_alias, ncol = 5) +
  labs(x="", fill="", y = "Proportion of total spots (%)", title="High M1 ATM") +
  theme_minimal() +
  geom_hline(yintercept = 0, color = "grey50") +
  theme(axis.text.x = element_text(angle = 90, vjust = 0.5),
        axis.text.y = element_text(size=16),
        axis.title.y = element_text(size=18),
        legend.position = "none", 
        panel.spacing = unit(2, "lines"),
        panel.grid.major.x = element_blank(),
        panel.grid.minor = element_blank()); p

fname <- paste0(ANALYSIS_ID, ".other_M1sign_bar")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 8, height = 4);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 8*2.5, height = 4*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2
p <- ggplot(subset(df_M1_prop, ATM_M1_cat == "high"), aes(x=as.factor(condition), y=pct)) +
  geom_boxplot(width=0.5) +
  geom_point(size=2, aes(color=subject_alias)) +
  # scale_color_gradient(low = colors_main[1], high = colors_main[2]) +
  scale_color_manual(values = colors_multi) +
  # ylim(min(d_plot$cluster_pct_subject), max(d_plot$cluster_pct_subject)) +
  scale_y_continuous(limits = c(0,30)) +
  # facet_grid(~subject_alias) +
  labs(y="Proportion of total spots (%)", title="High M1 ATM", x="") +
  theme_classic() +
  theme(legend.position = "none", plot.title = element_text(hjust=0.5, face = "bold"), 
        axis.text.x = element_text(size=10)); p

fname <- paste0(ANALYSIS_ID, ".other_M1sign_box")
pdf(useDingbats = F, file = file.path(DIR_FIG, paste0(fname, ".pdf")), width = 3, height = 3);p;dev.off()
## quartz_off_screen 
##                 2
tiff(filename = file.path(DIR_FIG, paste0(fname, ".tiff")), units = "cm", width = 3*2.5, height = 3*2.5, res = 600); p; dev.off()
## quartz_off_screen 
##                 2




Wrap up

Save object

fname <- paste0("se-object.", ANALYSIS_ID, ".rds")
saveRDS(object = se, file = file.path(DIR_RES, fname))

# se <- readRDS(file = file.path(DIR_RES, fname))



Session information

This analysis was last compiled on 2021-04-22.


sessionInfo()
## R version 3.6.3 (2020-02-29)
## Platform: x86_64-apple-darwin15.6.0 (64-bit)
## Running under: macOS Catalina 10.15.7
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRlapack.dylib
## 
## locale:
## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
## 
## attached base packages:
## [1] parallel  stats4    stats     graphics  grDevices utils     datasets 
## [8] methods   base     
## 
## other attached packages:
##  [1] org.Hs.eg.db_3.10.0         AnnotationDbi_1.48.0       
##  [3] rjson_0.2.20                rhdf5_2.30.1               
##  [5] knitr_1.30                  DT_0.16                    
##  [7] enrichplot_1.6.1            clusterProfiler_3.14.3     
##  [9] ReactomePA_1.30.0           clustree_0.4.3             
## [11] ggraph_2.0.3                harmony_1.0                
## [13] Rcpp_1.0.4.6                STutility_0.1.0            
## [15] SingleCellExperiment_1.8.0  SummarizedExperiment_1.16.1
## [17] DelayedArray_0.12.3         BiocParallel_1.20.1        
## [19] matrixStats_0.57.0          Biobase_2.46.0             
## [21] GenomicRanges_1.38.0        GenomeInfoDb_1.22.1        
## [23] IRanges_2.20.2              S4Vectors_0.24.4           
## [25] BiocGenerics_0.32.0         Seurat_3.1.5               
## [27] writexl_1.3.1               ggpubr_0.4.0               
## [29] patchwork_1.1.0             cowplot_1.1.0              
## [31] ggrepel_0.8.2               RColorBrewer_1.1-2         
## [33] ggplot2_3.3.2               tidyr_1.1.2                
## [35] Matrix_1.2-18              
## 
## loaded via a namespace (and not attached):
##   [1] rappdirs_0.3.1          coda_0.19-4             bit64_4.0.5            
##   [4] irlba_2.3.3             data.table_1.13.2       rpart_4.1-15           
##   [7] RCurl_1.98-1.2          doParallel_1.0.16       generics_0.1.0         
##  [10] Rvcg_0.19.1             RSQLite_2.2.1           RANN_2.6.1             
##  [13] europepmc_0.4           imager_0.42.3           future_1.20.1          
##  [16] bit_4.0.4               xml2_1.3.2              spatstat.data_1.4-3    
##  [19] webshot_0.5.2           httpuv_1.5.4            viridis_0.5.1          
##  [22] Morpho_2.8              xfun_0.18               hms_0.5.3              
##  [25] evaluate_0.14           promises_1.1.1          progress_1.2.2         
##  [28] readxl_1.3.1            igraph_1.2.6            DBI_1.1.0              
##  [31] htmlwidgets_1.5.2       spdep_1.1-5             purrr_0.3.4            
##  [34] ellipsis_0.3.1          crosstalk_1.1.0.1       dplyr_1.0.2            
##  [37] backports_1.2.0         ggiraph_0.7.8           deldir_0.1-29          
##  [40] vctrs_0.3.5             ROCR_1.0-11             abind_1.4-5            
##  [43] withr_2.3.0             ggforce_0.3.2           triebeard_0.3.0        
##  [46] checkmate_2.0.0         sctransform_0.2.1       prettyunits_1.1.1      
##  [49] goftest_1.2-2           cluster_2.1.0           DOSE_3.12.0            
##  [52] ape_5.4-1               lazyeval_0.2.2          crayon_1.3.4           
##  [55] labeling_0.4.2          pkgconfig_2.0.3         units_0.6-7            
##  [58] tweenr_1.0.1            nlme_3.1-149            rlang_0.4.8            
##  [61] globals_0.13.1          lifecycle_0.2.0         miniUI_0.1.1.1         
##  [64] dbscan_1.1-5            akima_0.6-2.1           rsvd_1.0.3             
##  [67] cellranger_1.1.0        bmp_0.3                 polyclip_1.10-0        
##  [70] lmtest_0.9-38           graph_1.64.0            tiff_0.1-5             
##  [73] urltools_1.7.3          raster_3.3-13           carData_3.0-4          
##  [76] Rhdf5lib_1.8.0          boot_1.3-25             zoo_1.8-8              
##  [79] ggridges_0.5.2          png_0.1-7               viridisLite_0.3.0      
##  [82] bitops_1.0-6            KernSmooth_2.23-17      blob_1.2.1             
##  [85] rgl_0.100.54            classInt_0.4-3          stringr_1.4.0          
##  [88] qvalue_2.18.0           manipulateWidget_0.10.1 parallelly_1.21.0      
##  [91] gridGraphics_0.5-0      jpeg_0.1-8.1            rstatix_0.6.0          
##  [94] ggsignif_0.6.0          reactome.db_1.70.0      scales_1.1.1           
##  [97] graphite_1.32.0         memoise_1.1.0           magrittr_2.0.1         
## [100] plyr_1.8.6              ica_1.0-2               gdata_2.18.0           
## [103] zlibbioc_1.32.0         compiler_3.6.3          fitdistrplus_1.1-1     
## [106] XVector_0.26.0          LearnBayes_2.15.1       listenv_0.8.0          
## [109] pbapply_1.4-3           MASS_7.3-53             mgcv_1.8-33            
## [112] tidyselect_1.1.0        stringi_1.5.3           forcats_0.5.0          
## [115] yaml_2.2.1              GOSemSim_2.12.1         grid_3.6.3             
## [118] fastmatch_1.1-0         tools_3.6.3             future.apply_1.6.0     
## [121] rio_0.5.16              uuid_0.1-4              foreach_1.5.1          
## [124] foreign_0.8-75          gridExtra_2.3           farver_2.0.3           
## [127] Rtsne_0.15              BiocManager_1.30.10     rvcheck_0.1.8          
## [130] digest_0.6.27           shiny_1.5.0             car_3.0-10             
## [133] broom_0.7.2             later_1.1.0.1           RcppAnnoy_0.0.17       
## [136] httr_1.4.2              gdtools_0.2.2           readbitmap_0.1.5       
## [139] sf_0.9-6                colorspace_2.0-0        tensor_1.5             
## [142] reticulate_1.18         splines_3.6.3           uwot_0.1.9             
## [145] expm_0.999-5            spatstat.utils_1.17-0   graphlayouts_0.7.0     
## [148] sp_1.4-4                ggplotify_0.0.5         plotly_4.9.2.1         
## [151] spData_0.3.8            systemfonts_0.3.2       xtable_1.8-4           
## [154] jsonlite_1.7.1          spatstat_1.64-1         tidygraph_1.2.0        
## [157] zeallot_0.1.0           R6_2.5.0                gmodels_2.18.1         
## [160] pillar_1.4.7            htmltools_0.5.0         mime_0.9               
## [163] glue_1.4.2              fastmap_1.0.1           class_7.3-17           
## [166] codetools_0.2-16        fgsea_1.12.0            tsne_0.1-3             
## [169] lattice_0.20-41         tibble_3.0.4            curl_4.3               
## [172] leiden_0.3.5            colorRamps_2.3          gtools_3.8.2           
## [175] magick_2.5.0            zip_2.1.1               GO.db_3.10.0           
## [178] shinyjs_2.0.0           openxlsx_4.2.2          survival_3.2-7         
## [181] rmarkdown_2.5           munsell_0.5.0           e1071_1.7-4            
## [184] DO.db_2.9               GenomeInfoDbData_1.2.2  iterators_1.0.13       
## [187] haven_2.3.1             reshape2_1.4.4          gtable_0.3.0
se@commands
## $SCTransform.RNA
## Command: SCTransform(se, variable.features.n = n_var_feat, verbose = T)
## Time: 2020-08-13 20:49:34
## assay : RNA 
## new.assay.name : SCT 
## do.correct.umi : TRUE 
## variable.features.n : 7000 
## variable.features.rv.th : 1.3 
## do.scale : FALSE 
## do.center : TRUE 
## clip.range : -30.51612 30.51612 
## conserve.memory : FALSE 
## return.only.var.genes : TRUE 
## seed.use : 1448145 
## verbose : TRUE 
## 
## $RunPCA.SCT
## Command: RunPCA(object = se, verbose = T)
## Time: 2020-08-13 20:56:26
## assay : SCT 
## npcs : 50 
## rev.pca : FALSE 
## weight.by.var : TRUE 
## verbose : TRUE 
## ndims.print : 1 2 3 4 5 
## nfeatures.print : 30 
## reduction.name : pca 
## reduction.key : PC_ 
## seed.use : 42 
## 
## $RunICA.SCT
## Command: RunICA(object = se, verbose = T)
## Time: 2020-08-13 21:18:17
## assay : SCT 
## nics : 50 
## rev.ica : FALSE 
## ica.function : icafast 
## verbose : TRUE 
## ndims.print : 1 2 3 4 5 
## nfeatures.print : 30 
## reduction.name : ica 
## reduction.key : IC_ 
## seed.use : 42 
## 
## $Seurat..ProjectDim.SCT.harmony
## Command: Seurat::ProjectDim(object, reduction = reduction.save, overwrite = TRUE,     verbose = FALSE)
## Time: 2020-08-13 21:54:11
## reduction : harmony 
## assay : SCT 
## dims.print : 1 2 3 4 5 
## nfeatures.print : 20 
## overwrite : TRUE 
## do.center : FALSE 
## verbose : FALSE 
## 
## $RunUMAP.SCT.harmony
## Command: RunUMAP(object = se, dims = dims_use, n.components = 3,     reduction = red_use, n.neighbors = nneigh, reduction.name = "umap3d")
## Time: 2020-08-13 21:58:44
## dims : 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 
## reduction : harmony 
## assay : SCT 
## umap.method : uwot 
## n.neighbors : 50 
## n.components : 3 
## metric : cosine 
## learning.rate : 1 
## min.dist : 0.3 
## spread : 1 
## set.op.mix.ratio : 1 
## local.connectivity : 1 
## repulsion.strength : 1 
## negative.sample.rate : 5 
## uwot.sgd : FALSE 
## seed.use : 42 
## angular.rp.forest : FALSE 
## verbose : TRUE 
## reduction.name : umap3d 
## reduction.key : UMAP_ 
## 
## $RunUMAP.SCT.ica
## Command: RunUMAP(object = se_ori_new, reduction = "ica", dims = dims_use,     n.neighbors = nneigh, reduction.name = "umapICA", seed.use = 42)
## Time: 2020-11-23 11:05:29
## dims : 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 
## reduction : ica 
## assay : SCT 
## umap.method : uwot 
## n.neighbors : 50 
## n.components : 2 
## metric : cosine 
## learning.rate : 1 
## min.dist : 0.3 
## spread : 1 
## set.op.mix.ratio : 1 
## local.connectivity : 1 
## repulsion.strength : 1 
## negative.sample.rate : 5 
## uwot.sgd : FALSE 
## seed.use : 42 
## angular.rp.forest : FALSE 
## verbose : TRUE 
## reduction.name : umapICA 
## reduction.key : UMAP_ 
## 
## $FindNeighbors.SCT.harmony
## Command: FindNeighbors(object = se, verbose = T, reduction = red_use,     dims = dims_use)
## Time: 2020-12-02 15:02:54
## reduction : harmony 
## dims : 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 
## assay : SCT 
## k.param : 20 
## compute.SNN : TRUE 
## prune.SNN : 0.06666667 
## nn.method : rann 
## annoy.metric : euclidean 
## nn.eps : 0 
## verbose : TRUE 
## force.recalc : FALSE 
## do.plot : FALSE 
## graph.name : SCT_nn SCT_snn 
## 
## $FindClusters
## Command: FindClusters(object = se, verbose = T, algorithm = 1,     resolution = res)
## Time: 2020-12-02 15:03:49
## graph.name : SCT_snn 
## modularity.fxn : 1 
## resolution : 2 
## method : matrix 
## algorithm : 1 
## n.start : 10 
## n.iter : 10 
## random.seed : 0 
## group.singletons : TRUE 
## verbose : TRUE